p(HGNC:BCCIP) -| bp(GOBP:"cell proliferation")

Copyright (c) 2011-2012, Selventa. All rights reserved.

Furthermore, expression of BCCIPalpha inhibits breast and brain cancer cell growth, but fails to inhibit HT1080 cells and a non-transformed human skin fibroblast.

The expression of Bcl-xl was repressed in response to p53 induction.

Treatment of p53 induces 3-4 fold upregulation of TRAIL-R2 and Fas mRNA but not upon induction of p53-R175H.

a(SCHEM:Aspirin) -| tscript(p(SFAM:"TCF/LEF Family"))

These results strongly suggest that aspirin and indomethacin attenuate the transcription of beta-catenin/TCF-responsive genes, by modulating TCF activity without disrupting beta-catenin/TCF complex formation.

We investigated AFP gene regulation in AFP-GC by an active transcription factor, HNF1 (hepatocyte nuclear factor 1) and a repressive transcription factor, ATBF1 (AT motif binding factor 1).

Leptin treatment did not alter 11betaHSD1 activity in human hepatocytes, but increased activity in omental ASC [135.8 +/- 14.1% (leptin, 100 ng/ml); P = 0.08 vs. control (100%)]. Treatment with interleukin-1beta induced 11betaHSD1 activity and expression in sc and omental ASC in a time- and dose-dependent manner.

Treatment with tumor necrosis factor-alpha (TNFalpha) caused a dose-dependent increase in 11betaHSD1 activity in primary cultures of both sc [1743.1 +/- 1015.4% (TNFalpha, 10 ng/ml); P < 0.05 vs. control (100%)] and omental [375.8 +/- 57.0% (TNFalpha, 10 ng/ml); P < 0.01 vs. control (100%)] ASC, but had no effect on activity in human hepatocytes [90.2 +/- 2.8% (TNFalpha, 10 ng/ml); P = NS vs. control (100%)].

kin(p(HGNC:CAMK2G)) -> tscript(p(HGNC:MEF2A))

# Ariadne: Several studies have reported that phosphorylation by p38 mitogen- activated protein kinase, the Big mitogen-activated protein (MAP) kinase (BMK1), calmodulin-dependent protein kinase (CaMK) and PI3-kinase can transcriptionally activate both MEF2A and MEF2C isoforms ( 33 , 34 , 35 , 36 , 37 ). [Regulation]

a(CHEBI:pioglitazone) -| cat(p(RGD:Acsl4))

The thiazolidinedione (TZD) insulin-sensitizing drugs and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, troglitazone, rosiglitazone, and pioglitazone, strongly and specifically inhibited only ACS4

IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT).

tscript(p(HGNC:AR)) -> (p(HGNC:IL6) -> tscript(p(HGNC:STAT3)))

a(SCHEM:Bombesin) -> p(RGD:Mapk1,pmod(P))

Bombesin and SpD differentially stimulated the phosphorylation of ERK1 and ERK2 in BOR-15 cells.

a(SCHEM:Bombesin) -> p(RGD:Mapk3,pmod(P))

a(SCHEM:"Substance P") -| (a(SCHEM:Bombesin) -> a(SCHEM:Calcium))

SpD, a substance P analogue, inhibited bombesin induced increase in intracellular calcium.

p(HGNC:EGF) -> kin(p(SFAM:"MAPK Erk1/2 Family"))

The SHP2 PTPase activity is required for activation of the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein (MAP) kinase by EGF.

IGF1 induced phosphorylation of p38 (Mapk14) and was inhibited by SB202190 treatment prior to Igf1 stimulation.

bp(MESHPP:Obesity) positiveCorrelation sec(p(RGD:Tnf))

Final body weight, kidney weight, blood glucose and serum tumor necrosis factor-alpha (TNF-alpha) level were higher in OLETF rats than in LETO rats. Serum and kidney GPX activities were higher, but adipose tissue GPX activity was lower, in OLETF rats than in LETO rats

p(HGNC:NRG1) -> p(HGNC:CTNNB1,pmod(P,Y))

HRG Stimulates Tyrosine Phosphorylation of beta -Catenin through the PI 3-Kinase Pathway and Its Association with HER2-- Because HRG has been shown to activate several signaling pathways (4, 5, 7, 10, 36), we next examined the nature of the signaling pathway responsible for HRG-induced beta -catenin tyrosine phosphorylation. Our results showed that the HRG-increased phosphorylation status of the immunoprecipitated beta -catenin was completely reduced by blocking the PI 3-kinase pathway by pharmacological inhibitor LY294002 (PI3K inhibitor) and only modestly reduced by inhibition of the MAP kinase pathway with the chemical inhibitor PD98059 (MEK1 inhibitor) (Fig. 2A).

To examine whether HRG signaling results in increased nuclear translocation of beta -catenin, we co-stained control and HRG-activated (30 min) cells with E-cadherin- and beta -catenin-specific antibodies and analyzed by confocal microscopy (Fig. 1D). We found that in addition to an increase within the cytoplasm, there was a significant enhancement of beta -catenin immunostaining inside the nucleus of HRG-treated cells (Fig. 1, lower panel). This was accompanied by cell-shape changes with appearance of some beta -catenin and E-cadherin immunoreactivity at the cellular free edges (Fig. 1D, arrows). In contrast, in control untreated cells, beta -catenin was almost exclusively restricted at the level of intercellular junctions (Fig. 1D, upper panel).

kin(p(HGNC:ERBB2)) => complex(p(HGNC:ERBB2),p(HGNC:CTNNB1))

To investigate the potential interaction of Tiam1, HER2, and beta -catenin, cell lysates were immunoprecipitated with an anti-HER2 antibody, and the precipitated material was immunoblotted with different antibodies. We found no evidence of an association of Tiam1 with HER2 receptors (Fig. 2B). In contrast, there was a significant increase in the content of beta -catenin associated with activated HER2 receptor (Fig. 2B).

Table 2a. Genes whose expression is increased by nicotine stimulation

Table 2b Genes whose expression is decreased by nicotine stimulation

kin(p(HGNC:ATM)) => p(HGNC:BRCA1,pmod(P,S))

The main downstream targets (of BRCA1) identified so far are p53-responsive genes, including p21 and BcIX13. BRCA1 binds to BRCA2, p53, RAD51 and many other proteins involved in cell cycling and DNA-damage response14,15 (Fig. 2a). The involvement of BRCA1 in response to DNA damage is supported by extensive data, including evidence that BRCA1 is phosphorylated by the ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) proteins in response to DNA damage16,17, that cells without functional BRCA1 do not arrest in G2 after DNA damage and are deficient in transcription-coupled repair18,19, and that BRCA1 is part of the RAD50-MRE11-p95 complex, an essential component of recombination- mediated repair of DNA double-stranded breaks20.

complex(p(MGI:Pgf),p(MGI:Vegfa)) -> kin(p(MGI:Flt1))

PIGF might enhance the angiogenic response to VEGF by forming VEGF/PIGF heterodimers, which have been detected in tumors and are upregulated by hypoxia

p(HGNC:VAV1,pmod(P,Y)) => cat(p(HGNC:VAV1))

Inhibition of Syk activity by piceatannol prevents both in vitro and in vivo Vav tyrosine phosphorylation, its association with the regulatory subunit of phosphoinositide 3-kinase, and the nuclear modifications typically observed during granulocytic differentiation of this cell line.

Overexpression of the C/EBPbeta gene, a downstream effector in the IL-6 pathway, activated transcription from the haptoglobin promoter.

complex(p(HGNC:SMAD3),p(HGNC:SMAD4)) -| tscript(p(HGNC:CEBPB))

This was abolished by either a constitutively active form of activin A type IB receptor (CAactRIB) or by a combination of Smad3 and Smad4.

We studied IL-6-induced secretion of the acute phase protein haptoglobin by hepatoma cells.

kin(p(HGNC:ATM)) => p(HGNC:MDM2,pmod(P,S,395))

Progesterone, lipopolysaccharide, tumour necrosis factor-alpha, and interleukin-1beta significantly stimulated the expression of ENA-78 by ESC. ....The expression of ENA-78 was also detected in cyclic endometrium by immunohistochemistry.

Despite the critical role lipid droplets play in maintaining energy reserves and lipid stores for the cell, little is known about the regulation of the lipid or protein components within the lipid droplet. Although immunofluorescence of intact cells as well as Western analysis of isolated lipid droplets revealed that sterol carrier protein-2 (SCP-2) was not associated with lipid droplets, SCP-2 expression significantly altered the structure of the lipid droplet. First, the targeting of fatty acid and cholesterol to the lipid droplets was significantly decreased. Second, the content of several proteins important for lipid droplet function was differentially increased (perilipin A), reduced severalfold (adipose differentiation-related protein (ADRP), vimentin), or almost completely eliminated (hormone-sensitive lipase and proteins >93 kDa) in the isolated lipid droplet. Third, the distribution of lipids within the lipid droplets was significantly altered. Double labeling of cells with 12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-octadecanoic acid (NBD-stearic acid) and antisera to ADRP showed that 70, 24, and 13% of lipid droplets contained ADRP, NBD-stearic acid, or both, respectively. SCP-2 expression decreased the level of ADRP in the lipid droplet but increased the proportion wherein ADRP and NBD-stearic acid colocalized by 3-fold. SCP-2 expression also decreased the lipid droplet fatty acid and cholesterol mass (nmol/mg protein) by 5.2- and 6.6-fold, respectively. Finally, SCP-2 expression selectively altered the pattern of esterified fatty acids in favor of polyunsaturated fatty acids within the lipid droplet. Displacement studies showed differential binding affinity of ADRP for cholesterol and fatty acids. These data suggested that SCP-2 and ADRP play a significant role in regulating fatty acid and cholesterol targeting to lipid droplets as well as in determining their lipid and protein components.

a(CHEBI:"cytochrome c") -> bp(MESHPP:Apoptosis)
cat(p(MGI:Sod2)) -| (a(CHEBI:"cytochrome c") -> bp(MESHPP:Apoptosis))

Release of cytochrome c from mitochondria to cytosol is a critical step in the mitochondrial-dependent signaling pathways of apoptosis. The authors have reported that manganese superoxide dismutase (Mn-SOD) attenuated cytochrome c release and apoptotic cell death after focal cerebral ischemia (FCI). The current study revealed Mn-SOD might affect cytochrome c translocation and downstream caspase activation in the mitochondrial-dependent cell death pathway after transient FCI.

kin(p(HGNC:MAPK14)) => p(HGNC:CDC25B,pmod(P,S,309))

inhibition of p38 blocks the rapid initiation of the G2 checkpoint in both human and murine cells p38 binds and phosphorylates CDC25B at serines 309 and 361 and CDC25C at serine216, phosphorylation of these residues is required for binding to 14-3-3 proteins inhibition of p38 prevents both phosphorylation of CDC25B at serine 309 and 14-3-3 binding after ultraviolet radiation

p(MGI:Mapk14) => complex(p(MGI:Cdc25b),p(MGI:Ywhah))

these statements are all true for murine cells as well

kin(p(SFAM:"PRKA Family")) => p(HGNC:AANAT,pmod(P,T,31))

a(SCHEM:Estrogens) -> bp(GOBP:"cell proliferation")

Estrogens and insulin/insulin-like growth factor-I (IGF-I) are potent mitogens for breast epithelial cells and, when co-administered, induce synergistic stimulation of cell proliferation.

Subsequent stimulation with insulin or IGF-I alone failed to induce significant S-phase entry. However, these treatments increased cyclin D1, cyclin E, and p21 gene expression and induced the formation of active Cdk4 complexes but resulted in only minor increases in cyclin E-Cdk2 activity, likely due to recruitment of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/Cip1) into these complexes.

Lithium also increased the expression of p21(Cip), a cyclin-dependent kinase inhibitor, both at the protein and RNA levels.

tscript(complex(SCOMP:"AP-1 Complex")) => r(RGD:Timp1)

JunD, Fra2, and FosB as the predominant AP-1 DNA-binding proteins, and all three associate with an AP-1 sequence that is essential for activity of the tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter.

PRC activated NRF-1-dependent promoters in a manner similar to that observed for PGC-1

We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor beta-chain is important for IL-2-induced Gab2 phosphorylation.

a(CHEBI:estradiol) -> p(MGI:Raf1,pmod(P,S,259))

We demonstrated that lung myofibroblasts, incubated in the presence of E2, showed a rapid phosphorylation on serine-259 of Raf1 and tyrosine-204 of ERK1/2 MAP kinase at 15 min, by approximately 3- and 5-fold, respectively

kin(p(HGNC:MAPK3)) => p(HGNC:HSPB8,pmod(P,T,87))

gtp(p(MGI:Gnaq)) -> kin(complex(SCOMP:"p85/p110 PI3Kinase Complex"))

Expression of constitutively active Galpha q mutant in 3T3-L1 cells led to a decrease in IRS-1 protein and insulin stimulated IRS-1 phosphorylation but had no effect with WT-Galpha q, but this effect was blocked by pretreatment with LY294002 and rapamycin (inhibitors of Pi3-kinase and p70-S6 kinase respectively).

Histamine induces CD86 expression on immature DC in a dose-dependent (significant at 10(-7) M) and transient manner (maximal after 24-h stimulation).

HLF, which was deficient in the protein product of the retinoblastoma tumor-suppressor gene (pRb), responded most profoundly to troglitazone, showing an increased expression in not only p21, but also in p27 and in p18.

a(CHEBI:troglitazone) -| bp(GOBP:"G1/S transition of mitotic cell cycle")

These findings suggested that p21, p27, and p18 might be involved in troglitazone-induced cell-cycle arrest in human hepatoma cells.

a(CHEBI:acetaldehyde) -> (kin(p(SFAM:"PRKC Family")) -> kin(p(HGNC:RPS6KB1)))
kin(p(SFAM:"PRKC Family")) -> kin(p(HGNC:RPS6KB1))

These effects were completely prevented by calphostin C, a protein kinase C inhibitor.

kin(p(SFAM:"PRKC Family")) -> kin(p(HGNC:MAPK3))

p(HGNC:VEGFA) -> kin(p(SFAM:"AKT Family"))

Akt activation by VEGF and shear stress mediates phosphorylation of eNOS at serine 1179 to cause calcium independent NO generation

VEGF endogenous production may be upregulated in vascular smooth muscle cells by hypoxia, growth factors (bFGF and PDGF-BB), and cytokines

VEGF has been reported to inhibit HUVEC apoptosis by activating the antiapoptotic kinase Akt via a PI3K-dependent pathway

VEGF increases phosphorylation of VE-cadherin, the major component of endothelial intercellular adherens junctions, and of the tight junction proteins occludin and zonula occludens-1

Intact muscle denervation reduced calpain 3 mRNA expression by a factor of 5 to 10, while alpha-skeletal actin mRNA was reduced in a slower and less extensive manner

complex(p(MGI:Il12a),p(MGI:Il12b)) -> bp(GOBP:"inflammatory response")

The anti-IL-12 antibody treatment decreased the number of apoptotic cells and the degree of inflammation and fibrosis in lung tissue

WT-5 cells derived from TSU-Pr1 cells expressing NEP enzyme activity without tetracycline treatment resulted in a 3 to 4 fold increase in p21 cell cycle protein levels.

p53 accumulation resulted in a gradual and dramatic loss of MGMT mRNA, protein, and enzyme activity, whose levels were undetectable by day 3 of induction. The loss of MGMT protein was, however, not due to its degradation because the ubiquitin-promoted in vitro degradation of MGMT, which mediates the cellular disposal of the repair protein, was not altered by p53.

p(MGI:Eif2ak2) -> (p(MGI:Pdgfb) -> kin(p(MGI:Mapk3)))

since in PKR-null MEFs there is a marked defect in Erk1 and Erk2 activation by PDGF (Figure1D), it appears that PKR is involved in serine phosphorylation of Stat3 through the activation of Erks.

IFNA treatment induced a strong activation of Rac1. An increase in the GTP bound Rac was observed in the BCR.ABL expressing KT-1 cells induced by IFNA.

complex(p(HGNC:FRS2),p(HGNC:GRB2),p(HGNC:GAB1)) -> kin(complex(SCOMP:"p85/p110 PI3Kinase Complex"))

assembly of FRS2alpha:Grb2:Gab1 complex induced by FGF stimulation results in activation of PI3-kinase and downstream effector proteins such as the S/T kinase Akt, whose cellular localization and activity are regulated by products of PI3-kinase.

The enhancing effect of Pit-1 was much lower for the GHS-R promoter than for 344 nucleotides of the human GH promoter, in agreement with the significantly lower expression levels of the GHS-R in somatotroph pituitary cells.Thyroid hormone and estrogen lead to a significant stimulation; glucocorticoids lead to a significant inhibition.

cat(p(HGNC:AGTR1)) -> kin(p(HGNC:MAPK10))
p(HGNC:ARRB2) -> (cat(p(HGNC:AGTR1)) -> kin(p(HGNC:MAPK10)))

Recently, we identified the c-Jun N-terminal kinase 3 (JNK3) as a beta-arrestin2-interacting protein in yeast-two hybrid and co-immunoprecipitation studies. Beta-arrestin2 acts as a scaffold to enhance signaling to JNK3 stimulated by overexpression of the MAP3 kinase ASK1 or by agonist activation of the angiotensin 1A receptor

p(HGNC:MAPK10,pmod(P)) => kin(p(HGNC:MAPK10))

The data also indicate that the specific step enhanced by beta-arrestin2 involves phosphorylation of JNK3 by the MAP2 kinase MKK4

a(CHEBI:cisplatin) -| path(SDIS:"tumor growth")

Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer. MCJ expression was associated with enhanced sensitivity to paclitaxel, topotecan, and cisplatin, suggesting that MCJ loss may play a role in de novo chemoresistance in ovarian carcinoma.

a(CHEBI:paclitaxel) -| path(SDIS:"tumor growth")

We show that Foxp1 and Foxp2 act as transcriptional repressors that are able to repress the mouse CC10 and human SP-C promoters to differing degrees.

kin(p(SFAM:"PRKC Family")) -> cat(p(HGNC:FCGR3B))

Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove FcgammaRIIIb also decreased phagocytosis of SAP-opsonized zymosan, but not CRP-opsonized zymosan.

complex(p(HGNC:APCS),p(HGNC:FCGR3B)) -> bp(GOBP:phagocytosis)

Zymosan was used to test the functional consequences of SAP and CRP binding to FcgammaR. Both SAP and CRP bound to zymosan and enhanced its uptake by PMN. This enhanced phagocytosis was abrogated by treatment of PMN with wortmannin, a phosphatidylinositol-3 kinase inhibitor, or with piceatannol, a Syk inhibitor, consistent with uptake through FcgammaR.

Treatment of 50ng/ml NGF for 48 hours increased approximately four-fold APP promoter activity (this induction is mediated by DNA sequences located between the nucleotides -307 and -15). Incubation of PC-12 cells with NGF for 48 hours lead to an increase in the intracellular APP content. Treatment of PC-12 subclone M-M17-26 (which express the dominant inhibitory RAS mutant) with NGF was not able to stimulate the APP promoter activity, showing the requirement of the functional Ras for this response.

kin(complex(SCOMP:"p85/p110 PI3Kinase Complex")) -| r(HGNC:IRS2)

A PI3K-specific inhibitor, LY294002, also upregulated IRS-2,

p(HGNC:EGF) -> kin(p(SFAM:"AKT Family"))

Activation of Akt is stimulated by a variety of growth factors, such as insulin, insulin-like growth factor 1 (IGF-1), platelet-derived growth factor, and epidermal growth factor

a(SCHEM:"serum insulin") -> kin(p(SFAM:"AKT Family"))

phos(p(HGNC:PTEN)) -| kin(complex(SCOMP:"p85/p110 PI3Kinase Complex"))

PTEN is a tumor suppressor that antagonizes phosphatidylinositol-3 kinase (PI3K) by dephosphorylating the D3 position of phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3).

expression of the B-myc mRNA is highly dependent on the presence of androgens and testicular factors.

complex(p(HGNC:SMAD2),p(HGNC:TGIF1)) -| tscript(p(HGNC:SMAD2))

c-Jun, which enhances the association of Smad2 with the nuclear transcriptional corepressor TG-interacting factor (TGIF), thereby interfering with the assembly of Smad2 and the coactivator p300 in response to TGF-beta signaling

complex(complex(SCOMP:"Nfy Complex"),p(HGNC:KAT2B)) => tscript(complex(SCOMP:"Nfy Complex"))

Coimmunoprecipitation experiments demonstrated that NFY is associated with the histone acetylase P/CAF in vivo and that irradiation resulted in an increased association of NFY with coactivator P/CAF. We propose that irradiation induction of the VWF promoter involves a mechanism resulting in increased recruitment of the coactivator P/CAFto the promoter via the NFY transcription factor.

glucocorticoids stimulate gene expression of PPARalpha and of medium chain acyl-CoA dehydrogenase (MCAD, a PPARalpha target gene) 2- to 4-fold and 1.5-fold, respectively, and that addition of fatty acids in the culture media led to a 2.2-fold increase in MCAD mRNA

We found that MGP transcription is downregulated by retinoic acid and transforming growth factor beta (TGF beta) whereas it is upregulated by vitamin D3 and cyclic AMP.

bp(GOBP:"hyperosmotic response") -> r(RGD:Akr1b1)

Like SMIT, BGT1 and AR genes, TauT, CDO and CSD genes appear to be tonicity-sensitive genes which can be activated in vivo by hypertonicity in the rat kidney

bp(GOBP:"response to osmotic stress") -> r(RGD:Cdo1)

Previously, we showed that overexpression of UCP-2 suppressed glucose-stimulated insulin secretion (GSIS) in isolated islets (1).

a(CHEBI:"insulin (human)") -> p(RGD:Mapk14,pmod(P))

Treatment of cells with insulin stimulated the phosphorylation of p38. The phosphorylation was stable and remained elevated for atleast 30 min.

a(SCHEM:"serum glucose") -> a(CHEBI:"reactive oxygen species")

Hyperglycemia increased reactive oxygen species generation in human platelets

a(SCHEM:"D-Glucose, anhydrous") -> a(SCHEM:"Advanced Glycation End Product")

AGE adducts in various tissues are known to progress as a function of age and glycemia, are associated with altered protein structure and function, and are able to generate reactive oxygen intermediates and induce cellular activation and inflammation (1,4).

Incubation with 100 microgram/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion.

tscript(p(HGNC:PPARA)) -| (p(HGNC:CRP) -> p(HGNC:CCL2))

The peroxisome proliferator-activated receptor-alpha activators fenofibrate (100 micromol/L) and Wy-14649 (100 micromol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-gamma activator ciglitazone had only a moderate effect.

kin(p(HGNC:SRC)) => p(HGNC:CTNND1,pmod(P,Y,302))

Here, as a first step toward pinpointing this role, we have employed two-dimensional tryptic mapping to directly identify the major sites of Src-induced p120 phosphorylation. Eight sites were identified by direct mutation of candidate tyrosines to phenylalanine and elimination of the accompanying spots on the two-dimensional maps. Identical sites were observed in vitro and in vivo, strongly suggesting that the physiologically important sites have been correctly identified. (Next section taken from Results - Fig 4) Mutation of tyrosines 112, 228, and 280 to phenylalanine resulted in elimination of phosphopeptide spots 6, 7, and 8, respectively. Mutation of tyrosine 96 eliminated spots 9 and 10, whereas mutation of tyrosine 257 eliminated spots 4 and 5...These results suggest that peptides 1, 2, and 3 represent singly, doubly, and triply phosphorylated variants, respectively, of the same peptide, containing Tyr291, Tyr296, and Tyr302.

The subsequent activation of Rac and Rho leads to the formation of focal complexes and focal adhesions, respectively.

tscript(p(HGNC:ZFPM2)) -| tscript(p(HGNC:NR2F2))

However, FOG-2 repressed transcriptional activation by GATA4-E215K in the presence of COUP-TF2, which demonstrates that FOG-2 can serve as a corepressor protein for COUP-TF2 on a cardiac-specific promoter..........The interaction between COUP-TF2 and FOG-2 in mammalian cells was confirmed by co-immunoprecipitation of these proteins from transfected COS-7 cells.

TGF-beta1 works antiatherogenically at early stages of diabetes by increasing NO production, whereas prolonged elevation of TGF-beta1 functions atherogenically by inhibiting endothelial cell growth

a(SCHEM:"serum leptin") -> p(HGNC:STAT3,pmod(P))

Additionally, incubation of endometrial specimens in the presence of leptin resulted in the phosphorylation of its intracellular target, STAT3 (signal transducer and activator of transcription 3).

p(HGNC:PGR) -> (a(CHEBI:progesterone) -| r(HGNC:LEPR))

These results indicate that, in the human endometrium, progestins act via the progesterone receptors to suppress functional OB-R(L) mRNA expression, and may thereby alter the sensitivity of the endometrium to leptin.

a(CHEBI:mifepristone) -| (a(CHEBI:progesterone) -| r(HGNC:LEPR))

This progestin-induced suppression was blocked by a concomitant addition of mifepristone.

The TG-induced Nur77 expression is also inhibited by overexpression of Cabin1, an endogenous inhibitor of calcineurin and a corepressor of the transcription factor MEF2, suggesting that MEF2 activation is required for Nur77 expression

complex(p(HGNC:DAB2),p(HGNC:SMAD3)) => tscript(p(HGNC:SMAD3))

TGFbeta stimulation triggers a transient increase in association of Dab2 with Smad2 and Smad3

phos(p(HGNC:DUSP4)) -| kin(p(HGNC:MAPK8))

MKP-2 preferentially inactivates extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) MAP kinase subfamilies

p(HGNC:ABL1) -> p(HGNC:PLSCR1,pmod(P,Y))

cat(p(HGNC:GFPT1)) -| tscript(p(HGNC:PDX1))

Overexpression of GFAT or treatment with glucosamine results in impaired glucose-stimulated insulin secretion and reduction in the expression levels of several beta-cell specific genes (insulin, GLUT2, and glucokinase). Additionally, the DNA binding activity of PDX-1, an important transcription factor for these three genes, was markedly reduced.

cat(p(HGNC:FRS2)) -> (kin(p(HGNC:RET)) -> kin(p(SFAM:"MAPK Erk1/2 Family")))
kin(p(HGNC:RET)) -> kin(p(SFAM:"MAPK Erk1/2 Family"))

However, overexpression of FRS2 but not Shc potentiates mitogen-activated protein (MAP) kinase activation by RET oncoproteins.

kin(p(HGNC:RET)) => p(HGNC:FRS2,pmod(P,Y))

In this report we demonstrate that the docking protein FRS2 is tyrosine phosphorylated by ligand-stimulated and by constitutively activated oncogenic forms of RET.

tport(p(MGI:Slc22a3)) -| a(SCHEM:Norepinephrine)

Two uptake systems that control the extracellular concentrations of released monoamine neurotransmitters such as noradrenaline and adrenaline have been described. The gene encoding the uptake-2 transporter has recently been identified in humans (EMT), rats (OCT3), and mice (Orct3/Slc22a3).

p(HGNC:PLCG1,pmod(P,Y)) => cat(p(HGNC:PLCG1))

SLP-76 is an adapter protein required for T-cell receptor (TCR) signaling. In particular, TCR-induced tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), and the resultant TCR-inducible gene expression, depend on SLP-76.

complex(p(HGNC:PLCG1),p(HGNC:LCP2)) => cat(p(HGNC:PLCG1))

The P-1 domain mediates a constitutive interaction of SLP-76 with the SH3 domain of PLC-gamma1 and is required for TCR-mediated activation of Erk, PLC-gamma1, and NFAT (nuclear factor of activated T cells).

Consistent with these results, BMP-2 increases caspase-9 and caspase-3, -6, and -7 activity, and an anti-caspase-9 agent suppresses BMP-2-induced apoptosis.

complex(p(HGNC:MAP3K7),p(HGNC:HGS)) -> p(SFAM:"MAPK JNK Family")

We found that Hgs associated physically with transforming growth factor-beta-activated kinase 1 (TAK1) and p21-activated kinase 1 (Pak1), which mediate the activation of c-Jun N-terminal kinase and serum response factor, respectively, leading to transactivation via the serum-response element and cyclic AMP-response element.

p(HGNC:CTNNB1,pmod(P,Y)) -> tscript(p(SFAM:"TCF/LEF Family"))

Here we show that exposure to FGF-1 and FGF-2 leads to significant and dose-dependent increase in E-cadherin-dependent cell-cell adhesion, tubular differentiation, and a reduced capacity to invade collagen gels. FGF stimulation produces phosphorylation of E-cadherin and beta-catenin on tyrosine residues, as well as increased E-cadherin localisation to the cytoplasmic membrane and association with FGFR1 demonstrable by coimmunoprecipitation

Quantitative ELISA measurement revealed 50 ng/ml BMP-6 was able to significantly reduce IL-6 and IL-11 production from marrow stroma, P< 0.01.

p(MGI:Bmp4) -> bp(GOBP:"cell differentiation")

Recombinant CHL protein inhibited the BMP4-dependent differentiation of embryonic stem cells in vitro and interacted directly with BMPs, similar to chordin.

We show that both HSP60s activate the stress-activated protein kinases p38 and JNK1/2, the mitogen-activated protein kinases ERK1/2, and the I-kappaB kinase (IKK).

p(HGNC:AR,pmod(P,S,210)) => (p(HGNC:AKT1) -| tscript(p(HGNC:AR)))

A mutation at AR Ser-210 results in the reversal of Akt-mediated suppression of AR transactivation.

kin(p(HGNC:AKT1)) => p(HGNC:AR,pmod(P,S,790))

Here, we demonstrate that Akt phosphorylates the androgen receptor (AR) at Ser-210 and Ser-790.

kin(p(SFAM:"PDGFR Family")) -> bp(GOBP:"cell proliferation")

In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3beta protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression.

tscript(p(MGI:Stat3)) -> bp(GOBP:"cell proliferation")

kin(p(HGNC:IKBKB)) -> tscript(p(HGNC:RELA))

SC-514, a selective inhibitor of IKK2 reduced the level of translocation of p65 into the nucleus in IL-1beta treated Rheumatoid arthritic synovial fibroblast. EMSA and Western analysis revealed a reduction in the level of nuclease p65 in SC-514 treated cells, by 60 minutes post IL-1beta stimulation. By 90 minutes the SC-514 treated RASF cells demonstrated little nuclear staining compared with untreated cells suggesting that IKK2 is involved in the nuclear translocation of p65

a(CHEBI:"reactive oxygen species") -> r(HGNC:CTGF)

The results showed that CTGF was induced by reactive oxygen species such as hydrogen peroxide and hydroxyl radicals.

p(HGNC:IKBKB) -> complex(SCOMP:"Nfkb Complex")

IKK-beta brought about the activation of NFkB.

# Ariadne: UO-44 gene expression in the uterus is strictly regulated by estrogens, tamoxifen, and GH, whereas the pure antiestrogen ICI 182780 is inhibitory. [Expression]

kin(p(HGNC:MAP3K10)) -> kin(p(HGNC:MAP2K7))

We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling....[break] With respect to ordering the death pathway, dominant-negative forms of MKK4 and -7 and c-Jun are protective against death induced by MLK overexpression, placing MLKs upstream of these kinases.

Incubation of monocytes with IL-4 or IL-13 induced 11beta-HSD1 activity by up to 10-fold. IFN-gamma, a known functional antagonist of IL-4 and IL-13, suppressed the induction of 11beta-HSD1 by these cytokines.

Cells were treated with TRAIL and PC3-Hygro cells show activation of Caspase9 where as activation was not resulted in PC3-Bcl2 expressing cells. In addition to this when cells were treated with dominant negative FADD activation of all the caspases including caspase2 was inhibited.

p(HGNC:RB1,pmod(P)) => complex(p(HGNC:RB1),p(HGNC:SMARCA4))

Rb phosphorylation changes Rb pocket conformation Change in Rb pocket conformation allow Rb binding to BRG1

kin(p(HGNC:CDK2)) => p(HGNC:RB1,pmod(P))

Furthermore, the fork-head activin signal transducer (FAST-1), known to interact with Smad2/Smad4 complexes, is a potent stimulator of TGFbeta1-induced transactivation of the fur P1 promoter.

path(SDIS:"tissue damage") -> r(RGD:Ap2b1)

Isolation and Sequence Analysis of Nerve Injury-induced cDNA Clones Table I Examples of known genes identified by sequencing from the subtractive library

path(SDIS:"tissue damage") -> r(MGI:Akr1b8)

path(SDIS:"tissue damage") -> r(RGD:"Atp5h-ps1")

path(SDIS:"tissue damage") -> r(MGI:Col5a2)

path(SDIS:"tissue damage") -> r(RGD:Cryab)

path(SDIS:"tissue damage") -> r(RGD:Eef1a1)

path(SDIS:"tissue damage") -> r(RGD:Erbb3)

path(SDIS:"tissue damage") -> r(RGD:Hmgcs1)

path(SDIS:"tissue damage") -> r(RGD:Hsp90ab1)

path(SDIS:"tissue damage") -> r(RGD:Hspa1b)

path(SDIS:"tissue damage") -> r(RGD:Igf1)

path(SDIS:"tissue damage") -> r(MGI:Nagpa)

path(SDIS:"tissue damage") -> r(MGI:Pja1)

path(SDIS:"tissue damage") -> r(RGD:Prnp)

path(SDIS:"tissue damage") -> r(RGD:Psma3l)

path(SDIS:"tissue damage") -> r(RGD:Stx12)

path(SDIS:"tissue damage") -> r(RGD:"Mt-co1")

a(SCHEM:Tretinoin) -> complex(p(MGI:Thra),p(MGI:Rxra))

T3 and 9-cis-reinoic acid promote dimerization

a(SCHEM:Tretinoin) -> complex(p(MGI:Thra),p(MGI:Rxrg))

kin(p(HGNC:MAP3K5)) -> bp(MESHPP:Apoptosis)

We found that Raf-1 interacts with the proapoptotic, stress-activated protein kinase ASK1 (apoptosis signal-regulating kinase 1) in vitro and in vivo

a(CHEBI:androgen) -> (tscript(p(HGNC:AR)) -> tscript(p(HGNC:CREBBP)))
tscript(p(HGNC:AR)) -> tscript(p(HGNC:CREBBP))

AR dramatically increased the intrinsic transcriptional activity of the nuclear receptor coactivators glucocorticoid receptor-interacting protein-1 (GRIP1), cAMP response element-binding protein-binding protein, and p300 that are tethered to DNA.

a(CHEBI:androgen) -> (tscript(p(HGNC:AR)) -> tscript(p(HGNC:GRIP1)))
tscript(p(HGNC:AR)) -> tscript(p(HGNC:GRIP1))

In this study, we describe a novel ligand-dependent transactivation function for AR that is independent of its DNA binding ability. AR dramatically increased the intrinsic transcriptional activity of the nuclear receptor coactivators glucocorticoid receptor-interacting protein-1 (GRIP1), cAMP response element-binding protein-binding protein, and p300 that are tethered to DNA.

p(HGNC:TP53,sub(P,151,H)) =| tscript(p(HGNC:TP53))

Table 2 p53 mutants unable to discriminate between diÂ?erent p53 responsive elements

p(HGNC:TP53,sub(A,276,G)) =| tscript(p(HGNC:TP53))

Table 2 p53 mutants unable to discriminate between diÃ???erent p53 responsive elements

p(HGNC:TP53,sub(C,238,W)) =| tscript(p(HGNC:TP53))

Table 2 p53 mutants unable to discriminate between diÃ??erent p53 responsive elements

p(HGNC:TP53,sub(C,242,Y)) =| tscript(p(HGNC:TP53))

p(HGNC:TP53,sub(N,239,S)) =| tscript(p(HGNC:TP53))

p(HGNC:TP53,sub(G,266,E)) =| tscript(p(HGNC:TP53))

Table 3 EÂ?ect of temperature on the ability of p53 mutants to discriminate between diÂ?erent p53 responsive elements

p(HGNC:TP53,sub(Y,126,S)) =| tscript(p(HGNC:TP53))

p(HGNC:TP53,pmod(P)) => tscript(p(HGNC:TP53))

We concluded that H7 inhibits constitutive C-terminal phosphorylation of p53, which regulates its turnover in unstressed cells.

bp(MESHPP:Obesity) positiveCorrelation r(RGD:Pnpla3)

The expression of adiponutrin mRNA is also 50-fold elevated in genetically obese fa/fa rats, indicating a link between adiponutrin and obesity.

complex(p(HGNC:HBEGF),p(HGNC:EGFR)) => kin(p(HGNC:EGFR))

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a mitogen and chemotactic factor, binds to two receptor tyrosine kinases, erbB1 and erbB4

p(HGNC:HBEGF) -> bp(GOBP:"cell migration")

NRDc enhanced their migration in response to HB-EGF but not to EGF. Conversely, inhibition of endogenous NRDc expression in cells by antisense morpholino oligonucleotides inhibited HB-EGF-induced cell migration.

When overexpressed in cells, NRDc enhanced their migration in response to HB-EGF but not to EGF

The RBP-Jkappa protein binds directly to the endogenous p21 promoter and p21 expression is induced specifically by activated Notch1 through RBP-Jkappa-dependent transcription.

kin(p(HGNC:RPS6KA3)) -> tscript(p(HGNC:ESR1))

docking of p90 ribosomal S6 kinase 2 (Rsk2) to the hormone-binding domain (HBD) of estrogen receptor alpha (ERalpha) induces a conformational change that enhances the transcriptional activation function contained in the HBD A constitutively active mutant of Rsk2 specifically enhances ERalpha-mediated transcription by phosphorylation of Ser167 in ERalpha

Since endoglin promoter activity is stimulated by TGF-beta and this stimulation is located at the Sp1-containing proximal region, we have investigated the possible involvement of Sp1 in the TGF-beta-mediated induction.

The results from transient transfection and co-precipitation experiments suggest that 14-3-3tau activates MEF2D by competitively inhibiting HDAC4 from binding to MEF2D and thereby affects muscle cell differentiation.

complex(p(HGNC:YWHAQ),p(HGNC:MEF2D)) => tscript(p(HGNC:MEF2D))

We found that 14-3-3tau forms a complex with MEF2D in vivo and specifically enhances MEF2 transactivational activity.

a(SCHEM:"Tetradecanoylphorbol acetate") -> r(HGNC:TGM1)

HOXA7 overexpressed in normal keratinocytes attenuated the TPA-induced expression of TGM1.

In human keratinocytes, Oct-11/Skn-1a activates expression of the differentiation markers K10 ( 26 ) and the small proline-rich envelope protein SPRR2A ( 28 ), and Oct-6 inhibits expression of the proliferation-associated K5 and K14 genes ( 29 ), suggesting activation of differentiation.

a(CHEBI:estradiol) => complex(p(HGNC:FOXO3),p(HGNC:ESR1))

The related family members, FKHRL1 and AFX, also bound to ER alpha in the presence of beta-estradiol.

a(CHEBI:"polyunsaturated fatty acid") -| p(RGD:Il2)

Ariadne: Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat lymphocytes.

Foxf1 +/- mutation was accompanied by reduced expression of vascular endothelial growth factor (VEGF), the VEGF receptor 2 (Flk-1), bone morphogenetic protein 4 (Bmp-4), and the transcription factors of the Brachyury T-Box family (Tbx2-Tbx5) and Lung Kruppel-like Factor

kin(p(SFAM:"PRKC Family")) => p(HGNC:CYTH1,pmod(P,T,395))

p(HGNC:STAT1,pmod(P,S,727)) => tscript(p(HGNC:STAT1))

STAT1 must be phosphorylated on serine 727 to be fully active in transcription.

These results demonstrate that MLK3 can induce neuronal apoptosis in the presence of NGF and that its kinase activity is required for its proapoptotic effect.

% both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase

Treatment of cells with antagonists of the Caspase 1 (zLEVDfmk) and Caspase 13 (zLEEDfmk) inhibited both TNF alpha downregulation of AP2 alpha expression and TNF alpha induced cell death.

Treatment of cells with inhibitors of Caspase 2 (zVDAVADfmk) and Caspase 8 (zLETDfmk), moderately prevented the downregulation of AP2 alpha expression and also had only a moderate effect on apoptosis.

Transient transfection of A431 cells with dominant-negative Grb2 constructs has revealed that the Grb2-C-SH3 domain possesses a central role in cortactin phosphorylation in response to HGF/SF. Finally, tyrosine phosphorylation of cortactin was found uncoupled of endogenous c-Src kinase activity, thus further supporting the hypothesis that cortactin is a direct target of the MET kinase. We propose that cortactin may constitute a docking site for MET-derived signals within the cytoskeleton.

Caspase 3 and 8 activation was also detected in the neo control cells after treatment with TRAIL, demonstrating the rapid activation of the caspase cascade similar to that seen with other death receptors. Bcl-2 overexpression in these cells blocked activation of these caspases, suggesting that bcl-2 expression of human cancer cells may be a critical factor in the therapeutic efficacy of TRAIL.

We report here that PIAS1, PIAS3, and PIASy of the protein inhibitor of activated STAT (PIAS) family, which are expressed in human prostate, display distinct effects on AR-mediated gene activation in prostate cancer cells. While PIAS1 and PIAS3 enhance the transcriptional activity of AR, PIASy acts as a potent inhibitor of AR in prostate cancer cells

a(CHEBI:"hydrogen peroxide") -> cat(p(RGD:Akr1b1))

A selective epidermal growth factor (EGF) receptor kinase inhibitor, tyrphostin AG1478, significantly suppressed the hydrogen peroxide (H2O2)-induced increase in AR mRNA and enzyme activity

a(CHEBI:"hydrogen peroxide") -> r(RGD:Akr1b1)

kin(p(RGD:Map2k1)) -> (a(CHEBI:"hydrogen peroxide") -> r(RGD:Akr1b1))

PD98059, a specific inhibitor of ERK kinase (MEK1), reduced H2O2-induced AR expression. EGF alone elicited activation of ERK and induction of AR expression

bp(GOBP:"response to oxidative stress") -> r(RGD:Akr1b1)

We and others recently reported that aldose reductase (AR), the rate-limiting enzyme in the polyol pathway, was upregulated by reactive oxygen and nitrogen species in vascular smooth muscle cells

p(HGNC:ELK1,pmod(P)) => tscript(p(HGNC:ELK1))

Elk-1-dependent transactivation is regulated by phosphorylation at serine-383 and -389, and each of the MAPK has been shown to be competent to phosphorylate this nuclear factor at these residues in vitro (33, 34, 35, 36, 37).

cat(p(HGNC:TLR2)) -> (tscript(complex(SCOMP:"Nfkb Complex")) -> r(HGNC:NOS2))
tscript(complex(SCOMP:"Nfkb Complex")) -> r(HGNC:NOS2)

Transfection of wtTLR2 restored the responsiveness of HMEC to PSM, STF, and OspA-L, as measured by NF-{kappa}B-dependent ELAM-promoter reporter (Fig. 1A), iNOS (Fig. 1B), and IL-8 promoter-reporter gene activation (Fig. 1C).

path(SDIS:"tissue damage") -> complex(p(HGNC:CLU),a(CHEBI:cholesterol))

Ariadne: In the central nervous system (CNS) only apoE and apoJ have been proposed to be responsible for the recycling of cholesterol after injury

tscript(p(MGI:Runx1)) -> path(SDIS:"Fetal Liver Hematopoiesis")

the transcription factor AML-1 has been described as a master regulator of hematopoiesis recent studies with gene-depleted mice suggest that AML-1 serves an essential, central function in development of all hematopoietic lineages

kin(p(HGNC:MAPK8)) -> cat(p(HGNC:CASP3))

This caspase activation and apoptotic changes occur through JNK

The increase in TNF-alpha mRNA and protein expression induced by insulin in THP-1 derived macrophage was markedly inhibited by pre-treatment of the cells with PD98059, which is a specific inhibitor of ERK-1 and ERK-2, at a concentration of 25 micro M.

p(HGNC:CRKL,pmod(P,Y)) -> kin(p(SFAM:"MAPK Erk1/2 Family"))

Overexpression of Lyn induced constitutive phosphorylation of CrkL and activation of Erk, whereas that of a Lyn mutant lacking the tyrosine kinase domain attenuated the Epo-induced phosphorylation of CrkL and activation of Erk. Furthermore, Lyn, but not Jak2, phosphorylated CrkL on tyrosine in in vitro kinase assays. Together, the present study suggests that, upon Epo stimulation, CrkL is recruited to the EpoR through interaction between the CrkL SH2 domain and phosphorylated Tyr(460) in the EpoR cytoplasmic domain and undergoes tyrosine phosphorylation by receptor-associated Lyn to activate the downstream signaling pathway leading to the activation of Erk and Elk-1.

Overexpression of all four isoforms of mouse NFI protein (NFI-A, -B, -C, and -X) suppressed both constitutive and heavy metal-induced activation of the MT-I promoter in HepG2 cells.

unlike other target genes of NFI, direct interaction of NFI with MT-I promoter is not necessary to mediate its repression. an NFI-C deletion mutant lacking the DNA binding domain continued to repress MT-I promoter. Overexpression of MTF-1, the key trails-acting factor involved in MT-I gene transcription, surmounted NFI-mediated repression of the basal and zinc-induced MT-I promoter activity. Interaction of NFI with another protein(s), probably MTF-I, may be involved in this repression.

a(SCHEM:"serum insulin") -> complex(p(MGI:Cyth3),p(MGI:Frmd4b))

When co-expressed in Chinese hamster ovary cells expressing the human insulin receptor, both proteins display a diffuse, cytoplasmic localization. Acute translocation and co-localization of GRSP1 (Frmd4b) and GRP1 (Pscd3)to ruffles in the plasma membrane was evident after insulin stimulation.

Ariadne: Overexpression of IRE1alpha and IRE1eta induced transcription of GRP78 and CHOP ( 27 , 28 ) and activated c-Jun NH 2 -terminal kinase (JNK ) ( 29 ), whereas a kinase-defective IRE1 down- regulated the UPR ( 27 , 28 ).

TNF? also induced in HUVEC, a marked time- and dose-dependent stimulation of SAPK2/p38 that is characterized by an increased activity of MAPKAP K2/3, a direct physiological target of SAPK2/p38 (21). Maximal stimulation was obtained after a 10-min exposure to concentrations of TNFalpha equal to or higher than 5 ng/ml (Fig. 3,A and B). The pyridinylimidazole derivative SB203580, in concentrations of 1?5 ?m, completely inhibited the TNFalpha-induced increase in SAPK2/p38 activity as reflected by the inhibition of MAPKAP K2/3 activation in cells exposed to TNFalpha (Fig. 3 C).

kin(p(HGNC:EGFR)) => p(HGNC:CBL,pmod(P,Y,371))

phosphorylation of c-Cbl on tyrosine 371 by the activated EGFR

a(SCHEM:"Testosterone propionate") -> r(HGNC:CCNB1)

CDK1 and CDK2, and cyclin A and cyclin B1 messenger RNAs were decreased 6 days after castration, increased 6-12 hours after TP treatment, and were expressed at high levels in recurrent CWR22 tumor

complex(p(HGNC:INHBA),p(HGNC:INHBA)) -| bp(GOBP:"cell growth")

suggest a role for activins in progression to malignancy, whereby, the normal growth inhibitory action of activin A observed on benign cells is lost with the acquisition of activin resistance in prostate cancer cells

kin(p(SFAM:"PRKC Family")) -> cat(p(HGNC:APEX1))

in vitro redox activity of APE/Ref-1 is stimulated by PKC phosphorylation. Furthermore, when human cells were exposed to the PKC activator phorbol 12-myristate 13-acetate, an increase in redox activity was observed that corresponded to an increase in the phosphorylation status of APE/Ref-1

p(HGNC:TGFB1) -| (p(HGNC:FGF2) -> tscript(p(HGNC:ETS1)))

When the DNA binding activity of Ets-1 protein was examined, bFGF was found to enhance DNA-Ets complex formation, whereas TGF-beta attenuated basal as well as bFGF-enhanced DNA-Ets complex formation. As a result, TGF-beta attenuated the promoter activity driven by Ets-1.

path(SDIS:"advanced Adenocarcinoma") -| r(MGI:Fzd3)

The molecular events leading to the development and progression of serous ovarian carcinoma are not completely understood. We performed a large scale survey for the identification of differentially expressed genes in serous ovarian carcinoma by using cDNA array analysis. Differences in gene expression between serous adenocarcinoma and benign serous adenoma, and between advanced and/or moderately or poorly differentiated and local, highly differentiated serous adenocarcinoma were assessed. The most striking difference between adenocarcinoma and benign adenoma was upregulation of RHOGDI2 in the carcinomas irrespective of the clinical tumor stage. Other changes in carcinoma were upregulation of MET and Ne-dlg, and downregulation of HGFAC, desmin, and PDGFA. The most prominent differences between advanced and local adenocarcinoma were upregulation of COL3A1, CFGR, and MET in advanced carcinoma, and downregulation of HGFAC, FZD3, and BFL1 in the same tumors. In conclusion, significant differences were found in the gene expression between benign and malignant serous ovarian tumors, and between local, highly differentiated and advanced and/or moderately or poorly differentiated serous adenocarcinomas. The differentially expressed genes may be related to the carcinogenesis and progression of the malignant growth.

path(SDIS:"advanced Adenocarcinoma") -| r(MGI:Hgfac)

path(SDIS:"advanced Adenocarcinoma") -> r(MGI:Met)

path(SDIS:"local Adenocarcinoma") -| r(MGI:Pdgfa)

IGF-I and IGF-II stimulated thymidine incorporation into DNA and suppressed apoptosis

a(CHEBI:lipopolysaccharide) -> tscript(complex(SCOMP:"Nfkb Complex"))

jubilant. Maximum active NF-kappaB was found at 30 min after the addition of LPS and decreased thereafter. (By aenayetallah)

bp(GOBP:"response to UV") -> kin(p(HGNC:MAPK8))

cells exposed to 10 J/m2 of UV showed phosphorylation of not only ERK1 and ERK2 but also JNK1/2 and p38 (Fig. 3).

Androgen treatment inhibited activation of caspases-8, -7, and -9

a(CHEBI:glucocorticoid) -> r(RGD:Sult1a1)

Concentration-response studies, coupled with a robust inhibition of glucocorticoid-inducible SULT1A1-5':luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486, recapitulated earlier findings on endogenous SULT1A1 gene expression and implicated a major role for the glucocorticoid receptor transcription factor in the regulation of glucocorticoid-inducible SULT1A1 gene expression.

IFN-gamma induced expression of P11 was blocked by JAK2 tyrosine kinase inhibitor.

p(HGNC:IFNG) -> kin(p(SFAM:"JAK Family"))

Treatment of AsPC-1, Capan-1, Capan-2 and Dan-G cells with 500 IU/ml IFN-gamma resulted in the activation of JAK1 phosphorylation. Bands of 130 kDa, phosphorylated Jak-1 and Jak-2 proteins, were first apparent after one minute of IFN-gamma stimulation and further increased at five minutes. A moderate increase in JAK1 and JAK2 phosphorylation was observed in Capan-2 cells.

kin(p(SFAM:"PRKC Family")) -> r(HGNC:CD69)

In this study the expression of C-type lectins during the early activation of PMA-stimulated peripheral blood lymphocytes was examined. To investigate the influence of de novo protein synthesis on activation-dependent expression of C-type lectins, cells were cultured in presence of cycloheximide (CHX) and mRNA levels were analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Upregulated levels of CD69, AICL, and LLT1, but less pronounced changes of CD161/NKR-P1A and CD94 mRNA were found at early time points of cellular activation.

The upregulation of TFAM and NRF-1, in aged skeletal muscle, appears involved in the pathway leading to the age-related increase of mitochondrial DNA content.

tscript(complex(SCOMP:"AP-1 Complex")) -| r(MGI:Npr3)

Activation of activator protein-1 (AP-1) was necessary, as shown by the inhibitory effect of curcumin and the results of the gel-shift assay.

The cGMP response to physiological concentrations of ANP was greater in EGF-treated D-NOD cells. These studies suggest that EGF potentiates the ANP glomerular effects in diabetes by inhibition of its degradation by mesangial NPR-C via a mechanism involving AP-1.

IGF1 stimulated c-Src and Fyn kinase activity. Fyn and c-Src were immunoprecipitated from IGF-1 stimulated proliferating cells at a peak stimulation time of 1 minute. IGF-1 stimulation of Fyn and c-Src was approximately 3 fold more than baseline.

kin(p(HGNC:IGF1R)) -> (kin(p(HGNC:SRC)) => p(HGNC:SHC1,pmod(P,Y)))
kin(p(HGNC:SRC)) => p(HGNC:SHC1,pmod(P,Y))

PP1 inhibited IGF-I phosphorylation of Shc but not of IRS-1.

Serum-starved 3T3-L1 cells with 10 nM IGF-I in the presence or absence of 10 mM PP1, a Src kinase inhibitor, for 24 h, resulted in inhibition of [3H]thymidine incorporation by IGF-I. Src plays a role in IGF-I-mediated 3T3-L1 mitogenesis.

path(MESHD:Ischemia) -> path(SDIS:"vascular tissue damage")

Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury.

leptin significantly inhibits the expression of steroidogenic acute regulatory protein in primary cultures of rat adrenocortical cells. This inhibition was observed at both the protein and mRNA levels.

cat(p(HGNC:MYD88)) -> kin(p(HGNC:IRAK1))

Schematic representation of NE-induced IL-8 signal transduction pathway in human bronchial epithelial cells. In bronchial epithelial cells, NE activates an as yet unidentified receptor. The cytosolic protein MyD88 acts as an adaptor coupling the receptor complex to IRAK. The signal is relayed downstream via TRAF-6 to the I?B kinases (IKKs) (via NIK/MEKK1), resulting in phosphorylation and degradation of I?B?, and subsequent release and translocation of NF?B to the nucleus where it transactivates IL-8 gene expression.

Here we show that DA induces apoptosis in SH-SY5Y neuroblastoma cells demonstrated by activation of caspase-9 and caspase-3, cleavage of poly(ADP-ribose) polymerase as well as nuclear condensation.

insulin activates the transcription of its own gene and that of the beta cell glucokinase gene (GCK) by different mechanisms

p(HGNC:INSR,pmod(P,Y)) -> kin(p(HGNC:RPS6KB1))

insulin gene transcription is promoted by signaling through insulin receptor type A, PI3K class Ia and p70s6k insulin stimulates the betaGK gene via insulin receptor B type, PI3K class II-like activity and PKB (Akt)

p(MGI:Tgfb1i1) -> bp(GOBP:"cell adhesion")

showed that Hic-5 inhibits integrin-mediated cell spreading on fibronectin in a competitive manner with paxillin in NIH 3T3 cells.

kin(p(HGNC:AKT1)) -> bp(GOBP:"cell cycle")

Overexpression of active Akt increased endothelial cell proliferation and, importantly, almost entirely compensated for serum depletioninduced cell cycle arrest (Fig. 8D).

Tat binding protein-1 synergistically activated the TR-mediated transcription with the steroid receptor coactivator 1, p120, and cAMP response element-binding protein, although Tat binding protein-1 did not directly interact with these coactivators in vitro.

p(HGNC:PSMC3) -> (p(HGNC:BRD8) -> tscript(p(HGNC:THRA)))

p(HGNC:PSMC3) -> (p(HGNC:CREBBP) -> tscript(p(HGNC:THRA)))

AIF induced apoptosis was completely inhibited by Bcl-2 over expression. The majority (65%) of Bcl-2 transfectants were protected from granulysin-induced cell death, mitochondrial membrane potential loss and AIF translocation.

Besides its direct angiogenic role, other potential mechanisms of the angiogenic function of IL-18 may be through IL-8 and other angiogenic cytokines that it up-regulates. Indeed, IL-18 exerts an inflammatory cytokine cascade in the mixed PBMC population by stimulating the constitutive expression of IL-18R on NK cells and lymphocytes, which leads to TNF-a production, ultimately stimulating macrophage IL-1b and IL-8 production (19). In turn, treatment with IL-1b and TNF-a of RA synovial fibroblast cultures, not constitutively expressing IL-18, induced IL-18 gene and protein production, suggesting a feedback interaction to promote Th1 cytokine and cell development in RA (21).

p(MGI:Il18) -> bp(GOBP:"blood vessel development")

However, the effect of IL-18 on basal proliferation, as examined in our study, was not explored. This group also found that murine, not human, IL-18 suppressed FGF-2-induced corneal neovascularization in mice, although the IL-18 was administered by i.p. injections, and it is unclear whether local rather than systemic treatment would have induced divergent results. Interestingly, they also found that IL-18 suppressed angiogenesis in the chick chorioallantoic membrane model. Our finding that IL-18 did not induce HMVEC proliferation is consistent with results obtained for other angiogenic mediators, such as soluble VCAM-1 or soluble E-selectin, which also do not induce endothelial proliferation (14). Consistent with the chemotactic properties of IL-18, we also showed IL-18 induction of HMVEC tube formation in Matrigel matrix in vitro. The degree of tube formation by IL-18 at 1 nM was comparable with the stimulant PMA (50 mM), a potent inducer of HMVEC differentiation and tube formation (51). In the Matrigel in vivo mouse angiogenesis model, IL-18 also stimulated actual blood vessel formation, which was visibly in excess of control.

IL-18 is also ascribed many inflammatory functions that would be consistent with a role in angiogenesis. For instance, IL-18 stimulates the production of other proangiogenic cytokines, such as TNF-a, IL-1b and IL-8, from human PBMCs, the responding cells being predominantly resting T cells and NK cells. IL-18 stimulation of the chemokine IL-8 has also been shown in the macrophage cell line derived from histiocytic lymphoma cell, U937, and the myelomonocytic leukemia cell line, KG-1 (44, 45), to produce IL-8 and other C-X-C chemokines.

Supportive of this function is the finding that IL-18 has been shown to stimulate production of angiogenic TNF-a (19).

Histamine, through H(2) receptors, triggers a prominent rise in intracellular free Ca(2+) concentration ([Ca(2+)](i)) in addition to an elevation of cAMP level

p(HGNC:TSC22D3) =| tscript(complex(SCOMP:"Nfkb Complex"))

Results indicate that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2 receptor expression and NF-kappaB activity

addition of 20 microM C(2)-ceramide to C2C12 myotubes for 3, 6 and 9 h resulted in increased UCP-3 and M-CPT-I mRNA levels.

Also, 1a,25(OH)2D3 inhibited expression of b-catenin?TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor g, Tcf-1, and CD44, whereas it induced expression of ZO-1.

gtp(p(HGNC:RAC1)) -> tscript(p(HGNC:STAT3))

cat(p(EGID:81638)) -> p(RGD:Tnni3,pmod(P,S))

Phosphorylation of troponin (Tn) I was increased in myocytes exposed to 25 mmol/l glucose. Losartan selectively inhibited Tn I serine phosphorylation

a(CHEBI:fenofibrate) -| a(SCHEM:"serum glucose")

All 3 compounds decreased serum glucose and triglyceride levels.

Fenofibrate and GW2331 induced expression of acyl-coenzyme A (CoA) oxidase and enoyl-CoA hydratase and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs.

Rosiglitazone modestly increased apolipoprotein C-III mRNA and had no effect on expression of the other 2 genes in the liver but increased the expression of glucose transporter 4 and phosphoenolpyruvate carboxykinase in adipose tissue.

tscript(p(RGD:Ppara)) -| a(SCHEM:Triacylglycerol)

we treated Zucker diabetic fatty rats (ZDF) for 15 days with a PPAR-alpha-specific compound, fenofibrate, a PPAR-gamma-specific ligand, rosiglitazone, and a PPAR-alpha/-gamma coagonist, GW2331, and measured the levels of several messenger RNAs (mRNAs) in liver by real-time polymerase chain reaction. All 3 compounds decreased serum glucose and triglyceride levels. Fenofibrate and GW2331 induced expression of acyl-coenzyme A (CoA) oxidase and enoyl-CoA hydratase and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs. Rosiglitazone modestly increased apolipoprotein C-III mRNA and had no effect on expression of the other 2 genes in the liver but increased the expression of glucose transporter 4 and phosphoenolpyruvate carboxykinase in adipose tissue. We identified a novel target in liver, mitogen-activated phosphokinase phosphatase 1, whose down-regulation by PPAR-alpha agonists may improve insulin sensitivity in that tissue by prolonging insulin responses

Compared to N and As lines, S lines also had diminished ability to grow in multi-layers and exhibited increased mRNA levels for plasminogen activator inhibitor-1 (PAI-1), secretory leukocyte protease inhibitor (SLPI), and tissue inhibitor of metalloproteinases (TIMP)-2.

In serum-free medium, S, but not N nor As lines, had enhanced DNA synthesis with transforming growth factor (TGF)-beta1, albeit all lines demonstrated similar responses to insulin-like growth factor-I and to epidermal growth factor, respectively.

IL-18 significantly enhanced ICAM-1 and VCAM-1 expression on endothelial cells and RA synovial fibroblasts. In addition, IL-18 induced E-selectin expression on endothelial cells and promoted the adhesion of HL-60 cells to IL-18-stimulated endothelial cells.

tscript(complex(SCOMP:"Nfkb Complex")) -> (p(HGNC:IL18) -> surf(p(HGNC:VCAM1)))

IL-18-induced adhesion molecule expression appears to be mediated through nuclear factor kappa B (NF kappa B) and phosphatidyl-inositol 3 kinase (PI 3-kinase) since addition of inhibitors to either NF kappa B (pyrrolidine dithiocarbamate and N-acetyl-l-cysteine) or PI 3-kinase (LY294002) inhibited RA synovial fibroblast VCAM-1 expression by 50 to 60%. Addition of both inhibitors resulted in inhibition of VCAM-1 expression by 85%

tscript(p(MGI:Nr3c1)) -| p(MGI:Hist1h1e,pmod(P))

H1 isoforms H1.0, H1.1, and H1.2 are non-responsive to hormone whereas prolonged dexamethasone treatment effectively dephosphorylated the H1.3, H1.4, and H1.5 isoforms.

kin(p(RGD:Stk17b)) -> bp(MESHPP:Apoptosis)

Overexpression of the rat homologue of DRAK2 caused apoptosis-like cell death of NIH3T3 cells

bp(GOBP:"mitotic G2 phase") -> r(HGNC:CDKN3)

Table I Genes with G2/M-specific and DNA damage-responsive expression: The relative increase in expression during G2 (as compared with S phase, i.e. at 7 h after release when compared with 1 h after release) is indicated in the third and fourth columns, and the average of these two independent analyses are in boldface type in the fifth column.

bp(GOBP:"mitotic G2 phase") -> r(HGNC:CCNL2)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:DNAJA1)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:HMMR)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:NCAPD2)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:PRPF38B)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:RPL27A)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:SLC39A10)

bp(GOBP:"mitotic G2 phase") -> r(HGNC:USPL1)

We have shown that sIL-6Ra levels released by myeloma cells are correlated with disease progression, explaining in part the strong prognostic value of sIL-6Ra serum levels in patients with MM [6]. Of major interest is the fact that the sIL-6Ra is an agonist of IL-6 able to potentiate its activity #[JL] the only way I can think of to model this is that IL6R^IL6, since IL6 doesn't have an activity in itself

kin(p(HGNC:PRKD3)) -> kin(p(HGNC:MAPK3))

we examined the requirement for PKCs in the PMA-induced activation of ERKs by using different PKC inhibitors. Treatment with GF109203X resulted in a total inhibition of ERKs activation, whereas rottlerin had no effect (Figure 8). Because rottlerin is unable to block the activation of ERKs by PMA, PKC-d is not implicated in this process. Given that atypical PKCs were not activated by PMA on the XG-6 cells, these results suggest that PKC-z was not involved...Finally, because XG-6 cells express PKC-nu and PKC-d as novel PKC isoforms, we can assume that the novel PKC, namely PCK-nu, is involved in the activation of ERKs by PMA.

bp(GOBP:"response to osmotic stress") -> r(HGNC:TNF)

we show that NFAT5 regulates expression of the TNFalpha and lymphotoxin-beta genes in osmotically stressed T cells. Chromatin immunoprecipitation experiments confirm that NFAT5 binds to the TNFalpha promoter in vivo.

a(CHEBI:"reactive oxygen species") -> r(HGNC:RGS2)

H2O2 increased RGS2 mRNA levels time- and concentration-dependently

a(CHEBI:estradiol) -> p(HGNC:MAPK1,pmod(P))

Furthermore, because of its capacity to inhibit the production and release of TNF-{alpha} and other proinflammatory cytokines by phagocytes in response to LPS, IL-10 reduces the lethality of experimental septic shock in mice

cat(p(HGNC:IL10RA)) -> tscript(p(HGNC:STAT3))

The ability of IL-10 to activate Stat3 tyrosine phosphorylation and SOCS-3 synthesis and to regulate IL-1 receptor antagonist and macrophage-inflammatory protein 1beta release in LPS-treated neutrophils correlated with this increased IL-10R1 expression, and was abolished by neutralizing anti-IL-10R1 and anti-IL-10R2 Abs.

TNF-alpha up-regulates the expression of 3 catalytic immunoproteasome subunits--LMP2, LMP7, and MECL-1--the immunomodulatory proteasome activator PA28 alpha, the TAP1/TAP2 heterodimer, and the total pool of MHC class I heavy chain.

a(SCHEM:Estrogens) -| complex(p(HGNC:ESR1),p(HGNC:BRCA1))

that BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor alpha (ERalpha), a principal determinant of the growth, differentiation, and normal functional status of breasts and ovaries. Ectopic expression in Brca1-deficient cells of wild-type BRCA1, but not clinically validated BRCA1 missense mutants, restored ligand-independent repression of ERalpha in a manner dependent upon apparent histone deacetylase activity. In estrogen-dependent human breast cancer cells, chromatin immunoprecipitation analysis revealed the association of BRCA1 with ERalpha at endogenous estrogen-response elements before, but not after estrogen stimulation.

Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl.

cat(p(HGNC:SST)) -| a(CHEBI:"nitric oxide")

SOM caused up-regulation of p53, Bcl-2, Fas and caspase-8 activities, and down-regulation of iNOS expression and NO production

a(CHEBI:histamine) -> complex(p(HGNC:RAB11FIP2),p(HGNC:RAB11A))

Rab11-FIP1, Rab11-FIP2, and pp75/Rip11 also coenriched with Rab11a and H(+)K(+)-ATPase on parietal cell tubulovesicles, and Rab11-FIP1 and Rab11-FIP2 translocated with Rab11a and the H(+)K(+)-ATPase upon stimulating parietal cells with histamine.

kin(p(HGNC:MAPK14)) => p(HGNC:TP53,pmod(P,S,33))

Activated p38(MAPK) phosphorylated endogenous p53 at Ser(33) in living cells.

a(CHEBI:"nitric oxide") -| r(MGI:Col1a1)

% Cardiac type I collagen mRNA expression was greater in control (P<0.01) and L-NAME-treated PAI-1(-/-) (P<0.05) groups than in control WT mice, indicating that PAI-1 deficiency prevents the increase of collagen deposition

Therefore, activated Notch1 appears to down-regulate the expression of SRG3 protein in the thymus.

BACKGROUND: The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat-1 (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression. METHODS: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter-reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPARalpha on the expression of ALDH2 by using PPARalpha-null mice. RESULTS: In vitro translated PPARs bound the ALDH NRRE with high affinity. Mutation of the NRRE indicated that binding was mediated by the DR-1 element. Cotransfection of PPAR expression plasmids showed that PPARalpha had no effect on expression of heterologous promoter constructs containing the NRRE. PPARgamma slightly induced expression, whereas PPARdelta repressed basal activity of the promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either stock rodent chow or a low-protein diet. Consistent with the transfection data, expression of ALDH2 protein was not different in PPARalpha-null mice. Treatment of the mice with the PPARalpha agonist WY14643 slightly decreased the level of ALDH2 protein in both wild-type and PPARalpha-null mice, suggesting that the effect of WY14643 was not mediated by the receptor. CONCLUSIONS: These data indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and proteins regulated by PPARalpha

a(SCHEM:"Tetradecanoylphorbol acetate") -| r(HGNC:EPCAM)

EpCAM expression, which is regulated negatively by TNFalpha and TPA through the activation of NF-kappaB

kin(p(SFAM:"AKT Family")) -> r(HGNC:VEGFA)

Transfection of the dominant negative Akt-K178A vector led to a 75% reduction in VEGF promoter activity in Hct116 cells and 60% in LoVo cells.

cat(p(HGNC:ICAM1)) -> (p(HGNC:IFNG) -> bp(GOBP:"cell adhesion"))
p(HGNC:IFNG) -> bp(GOBP:"cell adhesion")

Neutralizing antibodies against fractalkine or ICAM-1 significantly inhibited the basal and IFN- –induced adherence, and the treatment with both antibodies had a slight additive effect (Figure 5A).

bp(GOBP:"inflammatory response") -> p(HGNC:CX3CL1)

The results of immunofluorescent staining of biopsied bronchial tissues are shown in Figure 7. The bronchial epithelium in a section with inflammation, but not the normal-appearing epithelium, was stained positively for fractalkine.

kin(p(RGD:Prkg1)) -| p(RGD:Myl9,pmod(P,S,19))

In smooth muscle cells, one of the major receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell. These include proteins that regulate free intracellular calcium levels, the cytoskeleton, and the phosphorylation state of the regulatory light chain of smooth muscle myosin.

a(CHEBI:"thromboxane A2") -> bp(GOBP:vasoconstriction)

The prostanoids prostacyclin (PGI2)3 and thromboxane A2 (TXA2) play an essential role in the maintenance of vascular homeostasis. PGI2 is a vasodilator and an inhibitor of platelet aggregation, whereas TXA2 is a vasoconstrictor and a promoter of platelet aggregation

kin(p(SFAM:"PRKA Family")) -> p(HGNC:BRAF,pmod(P,S,428))

The Raf kinases serve as central intermediates to relay signals from Ras to ERK. Cell-specific effects of these signals on growth, differentiation and survival can be observed due to the recruitment of different isoenzymes of the Raf family. The in vitro phosphorylation of a site unique to B-Raf (Ser429) has been proposed to be responsible for the negative regulation of the isoenzyme by Akt. Using phosphopetide mapping and site-directed mutagenesis we showed that Ser429 is phosphorylated upon cAMP elevation in PC12 cells and proposed that PKA is a major kinase phosphorylating the B-Raf-specific site in vivo.

bp(GOBP:"response to hypoxia") -| cat(p(MGI:Kcna2))

several voltage-gated K+ channel subunits comprising 6 transmembrane segments and a single pore domain, Kv1.2, Kv1.5, Kv2.1, Kv3.1, Kv3.3, and Kv4.2, are reversibly blocked by hypoxia when expressed in heterologous expression systems

bp(GOBP:"response to hypoxia") -| cat(p(MGI:Kcnc3))

A dominant negative form of Shc carrying phenylalanine permutations at both tyrosines involved in Grb2 binding inhibited the activation of Rac in HUVECs plated on fibronectin in complete SFM.

cat(p(HGNC:ALOX5)) -| bp(MESHPP:Apoptosis)

Application of 5-LO or 5-LO activating protein-directed inhibitors, but not a cyclooxygenase inhibitor, reduced growth, increased apoptosis, down-regulated bcl-2, up-regulated bax

cat(p(HGNC:ALOX5)) -> bp(GOBP:"cell growth")

kin(p(HGNC:FLT1)) => p(HGNC:FLT1,pmod(P,Y,1242))

cat(p(HGNC:F2)) -> complex(p(HGNC:SPP1),p(HGNC:ITGA4),p(HGNC:ITGB1))

SVVYGLR has structural elements in common with other alpha(4) integrin-binding motifs and suggests why thrombin cleavage activates this motif.

bp(GOBP:"response to heat") -> r(HGNC:BAG3)

pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. bag-3 (bis, cair), which was identified as a bag-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with bcl-2. in this study we analyzed bag-3 expression in human pancreatic cancer tissues and cell lines. bag-3 mrna was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. in situ hybridization and immunohistochemistry analysis revealed that bag-3 was present in the cancer cells within the pancreatic tumor mass. when bag-3 mrna was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. in pancreatic cancer cells, bag-3 mrna expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (tnf)-alpha family (tnf-alpha, trail, fasl). these findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of bag-3 might function to block apoptosis. this characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo. in pancreatic cancer cells, bag-3 mrna expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (tnf)-alpha family (tnf-alpha, trail, fasl).

We report here that SPAK, a recently identified STE20/SPS1-related kinase that modulates p38 MAP kinase activity, exhibited increased expression in androgen-treated LNCaP cells. Androgen regulation of SPAK was both dose- and time-dependent. R1881-induced SPAK expression was completely abrogated by the antiandrogen casodex and by actinomycin D indicating that androgen induction of SPAK requires the androgen receptor and transcription

kin(p(HGNC:SRC)) => p(HGNC:GJA1,pmod(P,Y,247))

bp(GOBP:"response to UV") -> r(HGNC:RRM1)

UV irradiation of serum-starved, G0/G1-enriched mouse fibroblasts, stably transformed with an R1 promoter-luciferase reporter gene construct, caused a 3-fold increase in luciferase activity 24 h after irradiation, paralleled by an increase in the levels of R1 protein.

cat(p(MGI:Tnfrsf1a)) -> complex(SCOMP:"Nfkb Complex")

TNFR1 and TNFR2 negative mice had a blunted NFkB activation when compared with the wild-type controls, with the TNFR1 negative mice exhibiting the lowest levels of NF-kB binding activity after spinal cord injury. This indicates that TNFR1 and TNFR2 activate Nfkb.

kin(p(MGI:Lyn)) -> p(MGI:Ppp1r15a,pmod(P))

Lyn efficiently phosphorylated affinity-purified GADD34 in vitro. Lyn negatively regulated the proapoptotic function of GADD34 in a kinase-dependent manner. Expression of wild-type, but not kinase-inactive, Lyn weakened promotion of apoptosis by GADD34

IRAK is phosphorylated in response to IL-1

Preincubation for 30 min with U0126, a specific noncompetitive inhibitors of the p42/p44 ERK activators, MEK1 and MEK2 inhibited IL-1 beta induced release of GM-CSF, RANTES and eotaxin by 60-70%.

Treatment of proliferating SH-SY5Y cells with testosterone resulted in an up-regulation of alpha- and beta-tubulin We also show that an up-regulation of the ubiquitous beta(II)-tubulin and of the neurone-specific beta(III)-tubulin isoforms contributes to the overall increase in tubulin in response to androgen treatment

a(CHEBI:"reactive oxygen species") -> r(HGNC:PSMB6)

On the other hand, genes of three subunits of proteasome (PSMA2, PSMA3, PSMA4) were down-regulated by these antioxidants.

a(CHEBI:estradiol) -> p(HGNC:RB1,pmod(P))

No significant changes in protein kinase-mediated transcription factor activity could be detected here after estrogen stimulation of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb phosphorylation, all key events in cell cycle stimulation by mitogens, even in the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase (Mek)1/2 inhibitor.

tscript(p(HGNC:ATF2)) -> bp(MESHPP:Apoptosis)

Antisense Oligomers to c-Jun and ATF-2 but not to Elk-1 Reduce VES-induced Apoptosis.

Addition of transforming growth factor (TGF)-beta induced PG-I expression in HFL and HFFF2 fibroblasts as well as in the pancreatic cancer cell line PANC-1.

p(HGNC:MAPK1,pmod(P,T,185)) => kin(p(HGNC:MAPK1))

Full activation of ERK2 requires phosphorylation at both a threonine residue (Thr(183)) conserved in most protein kinases as well as a tyrosine residue (Tyr(185)) unique to members of the mitogen-activated protein kinase family.

Phosphorylation at Thr183 resulted in increases in the rate of phosphotransfer and the overall turnover rate, both of ?80-fold, and a partial (2.5-fold) restoration of the lowK m (MBP) displayed by [PP]ERK2. The increased catalytic commitment of MBP in response to phosphorylation at Thr183 is attributable mostly to the 80-fold increase in the rate of phosphoryl group transfer, as opposed to only minor changes in MBP binding affinity.

See Results; Activation of the Pparg pathway downregulates COX-2 protein expression.

kin(complex(SCOMP:"p85/p110 PI3Kinase Complex")) -> kin(p(HGNC:AKT1))

Fig. 6. VEGFR-2 or VEGFR-3 stimulation leads to PI3-kinase-dependent Akt phosphorylation.

bp(GOBP:"response to UV") -> r(HGNC:TYR)

it is the ubiquitous basic helix-loop-helix-leucine zipper transcription factor Usf-1 that is required for the UV activation of the Tyrosinase promoter.

complex(p(HGNC:RB1),p(HGNC:SUV39H1)) -| tscript(p(HGNC:E2F1))

We also found that Suv39H1 and Rb cooperate to repress E2F activity and that Suv39H1 could be recruited to E2F1 through its interaction with Rb.

tscript(p(HGNC:RB1)) =| tscript(p(HGNC:E2F1))

p(SFAM:"HDAC Family") -> tscript(p(MGI:Pou2f1))

Hdac inhibitors disrupt Oct1 binding to the octamer element Oct1 interacts with the H2A octamer element with a high efficiency and represses Ifng-inducible H2A promtoer activation in Rb-defective tumor cell lines the reduction in binding activity seen for Oct1 was specific, as 2 other proteins, Nfy and Yy1, were not affected in their ability to bind DNA following treatment of the cells with Hdac inhibitors

a(CHEBI:"trichostatin A") -> r(MGI:"H2-Eb2")
p(MGI:Ifng) -> (a(CHEBI:"trichostatin A") -> r(MGI:"H2-Eb2"))

the combination of TSA and Ifng treatments of cells also resulted in the rescue of Ifng-inducible H2A and H2-Eb2 mRNAs in these cells

cat(p(SFAM:"HDAC Family")) -| r(HGNC:"HLA-DRA")

treatment of these Rb-defective tumor cell lines with histone deacetylase, HDAC, inhibitors rescued IFN-gamma-inducible HLA-DRA and -DRB mRNA and cell surface protein expression, demonstrating repression of these genes by endogenous cellular HDAC activity

complex(p(HGNC:GRB2),p(HGNC:SOS1)) -> bp(GOBP:"cell proliferation")

To gain further insight into the importance of Grb2 for CML, peptides that disrupt Grb2-SoS complexes were tested. These high-affinity Grb2-binding peptides (HAGBPs) can autonomously shuttle into cells and function by binding to the N-terminal SH3 domain of Grb2. The HAGBPs were analyzed for their effects on Bcr-Abl-expressing cell lines and freshly isolated CML blast cells from patients. They induced a dramatic decrease in the proliferation of CML cell

IL-6 induced STAT3 transactivation was reduced from sixfold to 2.5-fold when cells were pre- treated with the JAK2 inhibitor (Figure 2b).

In prostate DU145 cells, both FGF1 and FGF2 activated ERK1/2 potently and p38 moderately.

bp(GOBP:"response to virus") -> r(HGNC:IFNA1)

Interferon alpha (IFN-alpha) is synthesized in response to viral infections. MxA protein, induced specifically by IFN-alpha and beta

p(HGNC:CXCL12) -> p(SFAM:"FOXO Family",pmod(P,S,256))

Sdf1 (cxcl12) increased mek, erk, rsk,akt, and creb, p-bad (112,136) phosphorylation in jurkat t cells within 7 or 20 min sdf treatment. Also apoptotic

ranscriptional response of selected cellular genes in Jurkat T cells upon SDF-1 exposure. Among the genes which showed a continuous increase in their expression following SDF-1 exposure were those involved in detoxification, DNA repair, apoptosis, TCR signal transduction, cytokinesis, cell adhesion molecules, chemokine receptors, and IFN-related molecules. The effects of MEK and PI3K inhibitors (50 µM PD098059 (20 21 ) and 20 µM LY294002 (22 ), respectively) on the expression of these genes are also shown. Jurkat cells were exposed to SDF-1 in the presence of the inhibitors for 6 h without FCS. Reference mRNA was obtained from cells exposed to the inhibitors but not to SDF-1. The expression ratios were determined as described in the legend to Fig. 1.

tscript(p(HGNC:STAT6)) -> bp(GOBP:"inflammatory response")

Allergic inflammatory conditions such as asthma are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-3/CCL26 is a member of the family of CC chemokines, which are known to be potent chemoattractants for eosinophils.......These results indicate that IL-4 and IL-13 activate eotaxin-3 gene expression in a STAT6-dependent fashion

tscript(p(MGI:Rb1)) -> phos(p(MGI:Alpl))

Following confluence, BMP-2was added tomedium at 200 ng/mL for 2-3 weeks, causing a 6-fold induction of ALP activity in wild-type MEFs. In RB/ MEFs, we observed a reduction in both basal and BMP-2-induced ALP activity as compared to that in wild-type MEFs, although BMP-2 still stimulated activity 3-fold in these cells (Figure 2A).

tscript(p(MGI:Rb1)) -> bp(GOBP:ossification)

MC3T3-E1 cells. Importantly, mineralization was not ob served in RB/ MEFs but was readily evident in MEFs lacking p107 or p130 (Figure 2D), suggesting that pRb in particular plays a critical role in late rather than early aspects of osteogenic differentiation.

tscript(p(HGNC:RB1)) -> bp(GOBP:ossification)

Several lines of evidence implicate pRb in osteogenesis. Viral oncoproteins that target the pocket proteins inhibit osteoblast differentiation.

These results suggest that POEM is a novel ligand for alpha(8)beta(1) integrin and that POEM may be involved in the development and function of various tissues, such as kidney, bone, muscles, and endocrine organs.

p(HGNC:TP53,pmod(P,S,15)) => tscript(p(HGNC:TP53))

The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of PRPK to COS-7 cells. PRPK was shown to bind to p53 and to phosphorylate p53 at Ser-15.

kin(p(HGNC:MAP2K2)) -> p(HGNC:MAPK1,pmod(P,Y,204))

PD98059--a specific inhibitor of MAP or Erk kinase 1 (MEK 1), the upstream kinase that phosphorylates Erk1/2--abolishes angiogenin-induced Erk phosphorylation and cell proliferation without affecting nuclear translocation of angiogenin.

Human lung carcinoma H460 cells were treated with AHPN (2.5 muM) or vehicle. After 8 h incubation, poly(A)+ RNA was isolated and used in cDNA-array screening. Egr-1, Nur77, GADD45, MyD118, GAD153, c-jun, c-fos, interferon response factor (IRF)-1, tristetraproline (TTP), and the cdk-inhibitor p21WAF1/Cip1 where among the genes identified by cDNA array screening.

a(SCHEM:CD437) -> p(HGNC:MAPK14,pmod(P))

Treatment with AHPN caused a rapid increase in the phosphorylation of p38 indicating that it is able to activate the p38 MAPK signaling pathway.

Individually both Lyn and Syk are required for maximal phosphorylation of CD22 following ligation of the BCR, and together Lyn and Syk are required for all of the constitutive and induced tyrosine phosphorylation of CD22.

cat(p(MGI:Pth1r)) -> a(SCHEM:"cyclic AMP")

tscript(p(MGI:Pparg)) -| bp(MESHPP:Apoptosis)

On the other hand, apoptosis is promoted by activation of Ppara in vascular smooth muscle cells and Pparg in human breast cancer cells, macrophages and vascular endothelial cells; however, apoptosis is suppressed by activation of Pparg in cerebellar granule cells.

kin(p(SFAM:"IkappaB Kinase Family")) -> r(HGNC:TNFSF10)

Tax stimulated TRAIL mRNA expression was almost completely blocked in the IKK-gamma deficient cells. This functional defect was largely rescued when the mutant cells were reconstituted with IKK-gamma.

cat(complex(p(HGNC:MBD3),p(HGNC:CHD4),p(HGNC:HDAC1),p(HGNC:HDAC2),p(HGNC:RBBP4),p(HGNC:RBBP7),p(HGNC:MTA2))) =| bp(GOBP:"histone acetylation")

whereas MBD3 is a subunit of the nucleosome remodeling histone deacetylase (NuRD ) complex that includes Mi-2, HDAC1/2, RbAp46/48, and metastasis-associated protein 2

p(HGNC:SOCS1) -| path(SDIS:"thrombopoietin activity")

p(HGNC:SOCS2) -| bp(GOBP:"insulin receptor signaling pathway")

dephosphorylation of NFATc1, MEF2A, and MEF2D transcription factors by calcineurin in all muscle types is dependent on nerve activity and positively correlated with muscle usage under normal weightbearing conditions.

phos(complex(SCOMP:"Calcineurin Complex")) =| p(MGI:Mef2d,pmod(P))

After bFGF was added to pulmonary fibroblasts, the kinase activities of p44/p42 ERK1/2 were determined by an in-gel assay at various times after exposure (Fig. 1). The data demonstrate that the addition of bFGF results in activation of ERK1/2 within 5 min, with the highest activity at 30 min, followed by a lower level of activity that persists for 8-12 h.

Figure 3A provides a gel shift analysis in which nuclear extracts isolated from bFGF-treated pulmonary fibroblast cultures were incubated with radiolabeled serum response element (SRE) of the c-Fos promoter. Several major complexes form, including two slow migrating complexes (complexes A and B) and several faster moving complexes (complex C). The addition of phosphorylated Elk-1 antibody abrogates the binding of complex B, demonstrating that phosphorylated Elk-1 is a component of complex B and, more importantly, showing that bFGF treatment results in the phosphorylation of Elk-1 (Fig. 3B).

However, plaque formation is also appreciated to be an inflammoratory response and it has been shown that activators of Pparg inhibit the production of inflammoratory cytokines such as TNFa, Il6 and Il1b.

tscript(p(MGI:Ppargc1a)) -> tscript(p(MGI:Nr3c1))

Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1.

a(SCHEM:"serum insulin") -| r(MGI:Ppargc1a)

PGC-1 reporter activity was blocked in cells treated with insulin

bp(GOBP:"response to hypoxia") -> r(HGNC:BNIP3)

they are hypoxically regulated in many tumor types, as well as in endothelial cells and macrophages. hypoxia induces up-regulation of BNIP3 and its homologue, Nip3-like protein X.

bp(GOBP:"response to hypoxia") -> r(HGNC:BNIP3L)

cat(p(HGNC:COMT)) -> a(SCHEM:"2-Methoxyestradiol")

Catechol-O-methyltransferase (COMT) catalyzes the methylation of catechol estrogens to methoxy estrogens, which simultaneously lowers the potential for DNA damage and increases the concentration of 2-methoxyestradiol (2-MeOE2), an antiproliferative metabolite

podocytes undergo apoptosis at early stages in the course of progressive glomerulosclerosis in TGF-beta1 transgenic mice.

complex(p(HGNC:MBL2),p(HGNC:CALR),p(HGNC:LRP1)) => bp(GOBP:phagocytosis)

Removal of apoptotic cells is essential for maintenance of tissue homeostasis, organogenesis, remodeling, development, and maintenance of the immune system, protection against neoplasia, and resolution of inflammation. The mechanisms of this removal involve recognition of the apoptotic cell surface and initiation of phagocytic uptake into a variety of cell types. Here we provide evidence that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin (also known as the cC1qR), which in turn is bound to the endocytic receptor protein CD91, also known as the alpha-2-macroglobulin receptor. Use of these proteins provides another example of apoptotic cell clearance mediated by pattern recognition molecules of the innate immune system. Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind.

trans-Activation of the intact CYP2C11 promoter (1.8-kilobase 5'-flank) was strongly induced by the liver nuclear factors HNF1alpha and HNF3beta but, unexpectedly, was inhibited by GH-activated STAT5b.

The amiloride-sensitive epithelial Na(+) channel (ENaC), which is made of three different but homologous subunits, controls the rate of transepithelial Na(+) absorption in a variety of epithelia. An 11-fold increase, induced by aldosterone, in the expression of the gamma subunit, but not in the alpha and beta subunits, was confirmed by capillary electrophoresis with laser-induced fluorescence (CE-LIF).

complex(p(HGNC:DTX1),p(HGNC:EP300)) -| tscript(p(HGNC:ASCL1))

Through its binding to p300, DTX1 inhibited transcriptional activation by the neural-specific helix-loop-helix-type transcription factor MASH1, and this mechanism is likely responsible for the differentiation inhibition of neural progenitor cells.

Treatment with forskolin increased the steady-state levels of ATA1 and ATA2 mRNAs, but decreased that of ATA3 mRNA.

a(SCHEM:"cyclic AMP") -> r(HGNC:SLC38A2)

kin(p(HGNC:ROCK1)) -> bp(GOBP:"regulation of vascular permeability")

Also depicted are other representative regulatory proteins whose activity either increases (green background) or decreases (white background) EC tension.

phos(p(HGNC:PTPN11)) -| p(HGNC:CTNNB1,pmod(P,Y))

An example of the complicated regulation of these adhesive sites is provided by the tyrosine phosphatase SHP2, which appears to help stabilize adherens junctions by decreasing tyrosine phosphorylation of catenins.

a(SCHEM:Calcium) -> bp(GOBP:"regulation of vascular permeability")

Left: schematic representation of the major components involved in regulating endothelial actomyosin contraction. Thrombin binding to its receptor increases intracellular Ca2+

bp(GOBP:"cell adhesion") -| bp(GOBP:"regulation of vascular permeability")

PULMONARY VASCULAR BARRIER REGULATION: OVERVIEW Despite recent therapeutic advances, inflammatory pulmonary conditions such as acute lung injury, acute respiratory distress syndrome, and sepsis continue to result in high rates of patient morbidity and mortality (3). Centrally involved in the pathogenesis of these processes and now recognized as a cardinal feature of inflammation, increased vascular permeability contributes to the profound pathophysiological derangements observed in these disorders. Because of the enormous surface area of the pulmonary vasculature, the pulmonary endothelium, which functions as a semipermeable cellular barrier between the vascular compartment and the interstitium, is particularly sensitive to the dynamic features of barrier regulation. Endothelial barrier properties are not uniform throughout the pulmonary vasculature, with greater macromolecule diffusion in postcapillary venules compared with pulmonary arterioles in whole lung models (91, 96, 118), whereas cultured microvascular endothelial cells (ECs) exhibit tenfold higher barrier properties than macrovascular EC as measured by electrical resistance across monolayers (13). Although the precise mechanisms that regulate this variability in segmental barrier function are unknown, barrier regulatory components such as Ca2+ signaling pathways and differences in content and regulation of barrier protective cAMP are likely involved (21, 80, 135). The integrity of the pulmonary EC monolayer is a critical requirement for preservation of pulmonary function, with two general pathways described for the movement of fluid, macromolecules, and leukocytes into the interstitium and subsequently the alveolar air spaces. The transcellular pathway utilizes a tyrosine kinase-dependent, gp60-mediated transcytotic albumin route, whose regulation and function are unclear but which may serve to uncouple protein and fluid permeability (103, 127, 143). However, there is general consensus that the primary mode of fluid and transendothelial leukocyte trafficking occurs by the paracellular pathway (Fig. 1), whose essential role in endothelial permeability has been well supported by an impressive body of research, including electron microscopy studies (69, 102), which demonstrate the formation of paracellular gaps at sites of active inflammation within the vasculature. View larger version (134K): [in this window] [in a new window] Fig. 1. Paracellular route of pulmonary inflammation. Under basal conditions, endothelial cells (ECs) of the pulmonary vasculature form a semipermeable barrier that restricts the flow of luminal contents into the alveolar air spaces. The important roles of flow and platelets/platelet-derived phospholipids in maintaining these intact intercellular junctions are becoming increasingly recognized (52, 147, 166, 167). During inflammation, the endothelium is activated by biophysical alterations (stretch or increased shear) or by stimuli such as thrombin, tumor necrosis factor (TNF), and/or reactive oxygen species to form paracellular gaps. In concert with a break in the EC barrier, fluid, proteins, and polymorphonuclear neutrophils (PMNs) flow into the alveoli to produce pulmonary edema via this paracellular route. Mechanistic approaches designed to understand EC paracellular gap formation and barrier function have revealed the complexity of these processes; however, several valuable paradigms have been developed. One useful model describes paracellular gap formation as regulated by the balance of competing contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which together regulate cell shape changes (53). As outlined in Fig. 2, both competing forces in this model are intimately linked to the actin-based endothelial cytoskeleton by a variety of actin-binding proteins that are critical to both tensile force generation as well a...

p(HGNC:TNF) -> bp(GOBP:"regulation of vascular permeability")

possibly through extracellular signal-regulated kinase (ERK)-catalyzed caldesmon phosphorylation and subsequent alteration of actomyosin cross bridging. Likewise, the cytokine TNF- through its receptor (TNF-R) appears to mediate cytoskeletal rearrangement and eventual barrier dysfunction through a PKC-dependent pathway. Although TNF- produces an increase in MLC phosphorylation, this effect does not appear to contribute to the subsequent increase in EC permeability.

kin(p(HGNC:ROCK1)) -| phos(p(HGNC:PPP1R12A))

whereas Rho kinase augments EC contraction by inhibiting both MLC phosphatase and the actin-depolymerizing protein, cofilin.

kin(p(HGNC:ATM)) => p(HGNC:H2AFX,pmod(P,S,140))

kin(p(MGI:Atm)) => p(MGI:H2afx,pmod(P,S,140))

The immunoprecipitated ATM efficiently phosphorylated recombinant H2AXin vitro (Fig. 3 c, lane 1).

Additionally, Mig and SDF-1alpha activated MAPKs p44/42 and p38 on melanoma cells.

cat(p(HGNC:CXCR4)) -> complex(p(HGNC:FN1),p(HGNC:ITGA5),p(HGNC:ITGB1))

Furthermore, the chemokine SDF-1alpha, the ligand of CXCR4, triggered modulation of beta(1) integrin-dependent melanoma cell adhesion to fibronectin.

the chemokine Mig, a ligand for CXCR3, activates the small GTPases RhoA and Rac1, induces a reorganization of the actin cytoskeleton, and triggers cell chemotaxis and modulation of integrin VLA-5- and VLA-4-dependent cell adhesion to fibronectin.

p(HGNC:VEGFA) -> kin(complex(SCOMP:"p85/p110 PI3Kinase Complex"))

Stimulation of cells with VEGF modestly increased PI3K activity over the basal levels as indicated by the phosphorylation of phospholipids. A significant increase in the PI3K activity was observed when heparin was present with VEGF in the T47D cells grown on plastic. A slightly higher intensity of VEGF-induced PI3K activity was observed in T47D cells grown on fibronectin. VEGF induced AKT activity was blocked when the PI3K inhibitor, LY294002 was added.

kin(p(RGD:Igf1r)) => p(RGD:Irs1,pmod(P,Y,658))

a(SCHEM:"serum glucose") -> p(RGD:Creb1,pmod(P,S,133))

Fibronectin contains cAMP responsive element (CRE) consensus sequences in its promoter and the phosphorylation of CRE-binding protein (CREB) may regulate its expression. On Western blots, HG and GlcN stimulate two- to threefold the phosphorylation of CREB at Ser 133, whereas CREB protein content was unaltered by either HG or GlcN.

a(SCHEM:"serum glucose") -> tscript(p(RGD:Creb1))

p(HGNC:CYP8B1) -> a(CHEBI:"cholic acid")

Cholesterol conversion to bile acids is subject to a feedback regulatory mechanism by which bile acids down-regulate their own synthesis. This regulation occurs at the level of transcription of several genes encoding enzymes in the bile acid biosynthetic pathway. One of these enzymes is sterol 12alpha-hydroxylase/CYP8B1 (12alpha-hydroxylase), the specific enzyme required for cholic acid synthesis.

complex(p(HGNC:NR0B2),p(HGNC:NR5A2)) =| tscript(p(HGNC:NR5A2))

Here, we report that the short heterodimer partner (SHP) suppresses 12alpha-hydroxylase promoter activity via an interaction with FTF. Hepatic nuclear factor-4 (HNF-4) binds and activates the 12alpha-hydroxylase promoter and is required for 12alpha-hydroxylase promoter activity.

IPF-1 also appears to mediate glucose-induced stimulation of insulin-gene transcription.

tscript(p(HGNC:PDX1)) -> (a(SCHEM:"serum glucose") -> r(HGNC:INS))

The MODY-associated transcription factors - hepatocyte nuclear f actor (HNF)4al (associated with MODY 1), HNF-1 alpha (MODY 3), insulin promoter factor 1 (IPF-1 [MODY 4]), HNF-1beta (MODY 5), and neurogenic differentiation factor 1 (NeuroD1), or beta-cell E-box transactivator 2 (BETA2 [MODY 6]) - function in the nucleus of the beta cell and regulate the transcription of the insulin gene (either directly, as in the case of HNF-1a, HNF-1b, IPF-1, and NeuroD1 or BETA2, or indirectly, through effects on the expression of other transcription factors, as in the case of HNF-4a

mild hyperglycemia leads to increased expression of the single wild-type gluco- kinase-gene allele, thus limiting the severity of the defect in glucose- stimulated insulin secretion.

bp(GOBP:"insulin secretion") -> (kin(p(HGNC:GCK)) -> sec(a(SCHEM:"D-Glucose, anhydrous")))
kin(p(HGNC:GCK)) -> sec(a(SCHEM:"D-Glucose, anhydrous"))

the decrease in insulin secretion was directly proportional to the decrease in the glucokinase-mediated flux of glucose

cat(complex(SCOMP:"T Cell Receptor Complex")) -> p(MGI:Il2)

The interaction of anti-TSA with FcgammaRIIB resulted in an inhibition of the ability of the FcgammaRIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-Cbeta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells.

(Jubilant) Downregulation of eNOS expression by thrombin was prevented by C3 exoenzyme, the specific inhibitor of Rho or by Y-27632, the specific inhibitor of ROCK, a downstream target of Rho suggesting the involvement of Rho/ROCK pathway in eNOS supression.

Incubation of human umbilical vein endothelial cells with thrombin (0.01 to 4 U/mL) for 15 to 24 hours markedly downregulated eNOS and increased ECE-1 protein level in a dose-dependent manner. Thrombin also decreased eNOS mRNA and increased ECE-1 mRNA level.

bp(GOBP:"response to hypoxia") -> r(RGD:Dusp1)

MKP-1 mRNA and protein levels were up-regulated by hypoxia

a(CHEBI:lipopolysaccharide) -> r(HGNC:CXCL6)

Five late LPS-activated chemokine genes (SCYB11, BLC, IP-10, GCP2, and MCP-2) listed in Fig. 3 show diminished up-regulation in cells pretreated with OxLDL.

a(CHEBI:lipopolysaccharide) -> r(HGNC:TNF)
a(SCHEM:"Oxidized Low Density Lipoprotein") -> (a(CHEBI:lipopolysaccharide) -> r(HGNC:TNF))

The RT-PCR data in Fig. 5a shows that OxLDL induces significant increases in the LPS activation of Mip-3, IL-8, Mip-1, IL-1, and TNF-.

cat(p(HGNC:PON2)) -| bp(GOBP:"response to oxidative stress")

Cells that overexpressed PON2 showed significantly less intracellular oxidative stress

cat(p(MGI:Gpx1)) -| bp(MESHPP:Apoptosis)

Glutathione peroxidase is an antioxidant enzyme that is involved in the control of cellular oxidative state. Recently, unregulated oxidative state has been implicated as detrimental to neural cell viability and involved in both acute and chronic neurodegeneration. In this study we have addressed the importance of a functional glutathione peroxidase in a mouse ischemia/reperfusion model. Two hours of focal cerebral ischemia followed by 24 h of reperfusion was induced via the intraluminal suture method. Infarct volume was increased three-fold in the glutathione peroxidase-1 (Gpx-1) -/- mouse compared with the wild-type mouse; this was mirrored by an increase in the level of apoptosis found at 24 h in the Gpx-1 -/- mouse compared with the wild-type mouse. Neuronal deficit scores correlated to the histologic data. We also found that activated caspase-3 expression is present at an earlier time point in the Gpx-1 -/- mice when compared with the wild-type mice, which suggests an enhanced susceptibility to apoptosis in the Gpx-1 -/- mouse. This is the first known report of such a dramatic increase, both temporally and in level of apoptosis in a mouse stroke model. Our results suggest that Gpx-1 plays an important regulatory role in the protection of neural cells in response to the extreme oxidative stress that is released during ischemia/reperfusion injury.

[Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

Gene-disease associations inferred from animal model manually asserted gene-disease associations.
DisGeNET evidence - PREDICTED

[LTP but not seizure is associated with up-regulation of AKAP-150.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Elevated expression of urotensin II and its receptor in diabetic cardiomyopathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Activation of signaling molecules and matrix metalloproteinases in right ventricular myocardium of rats with pulmonary hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Identification of gene expression profiles correlated to tumor progression in a preclinical model of colon carcinogenesis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1 and VEGF.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression of matrix metalloproteinases and inhibitors on the scleral tissue of lamina cribrosa in rat with experimental chronic ocular hypertension].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Identification of the apoptosis activation cascade induced in mammary carcinomas by energy restriction.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Greater stress protein expression enhanced by combined prostaglandin A1 and lithium in a rat model of focal ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Adenoviral-mediated uteroglobin gene transfer inhibits neointimal hyperplasia after balloon injury in the rat carotid artery.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Redox regulation of resveratrol-mediated switching of death signal into survival signal.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Distribution and kainate-mediated induction of the DNA mismatch repair protein MSH2 in rat brain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Synergistic activation of glucose-6-phosphate dehydrogenase and NAD(P)H oxidase by Src kinase elevates superoxide in type 2 diabetic, Zucker fa/fa, rat liver.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Blood pressure regulates the activity and function of the Na-K-2Cl cotransporter in vascular smooth muscle.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Microglial expression of chemokine receptor CCR5 during rat forebrain development and after perinatal hypoxia-ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Gelsolin immunoreactivity and development of the tectorial membrane in the cochlea of normal and hypothyroid rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Down-regulation of lipoprotein lipase and VLDL receptor in rats with focal glomerulosclerosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[An atherogenic lipid profile with low serum paraoxonase-1 activity during nematode infection in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Role of FTY720 on M1 and M2 macrophages, lymphocytes, and chemokines in 5/6 nephrectomized rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[A rodent model for Wilms tumors: embryonal kidney neoplasms induced by N-nitroso-N'-methylurea.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Characterizing the role of MDM2 in diethylnitrosamine induced acute liver damage and development of pre-neoplastic lesions.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Minocycline reduces neuronal death and attenuates microglial response after pediatric asphyxial cardiac arrest.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Changes of bone morphogenetic protein-7 and inhibitory Smad expression in streptozotocin-induced diabetic nephropathy rat kidney].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Activation of the stress protein response prevents the development of pulmonary edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion injury in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Folic acid pretreatment prevents the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Regulation of MT melatonin receptor expression in the foetal rat pituitary.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of olmesartan on tissue expression balance between angiotensin II receptor and its inhibitory binding molecule.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Cloning of rat interleukin-3 receptor beta-subunit from cultured microglia and its mRNA expression in vivo.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Minocycline modulates chemokine receptors but not interleukin-10 mRNA expression in hypoxic-ischemic neonatal rat brain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Development of beta-cells in the native pancreas after pancreas allo-transplantation in the Spontaneously Diabetic Torii rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Imbalance of RANK, RANKL and OPG expression during tibial fracture repair in diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Hypertension associated with reduced plasma thrombomodulin levels and a hypercoagulable state in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[A Tyrosinase missense mutation causes albinism in the Wistar rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The study of thrombospondin-I (TSP1) expression in the early stages of diabetic retinopathy induced by streptozotocin].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[A thrombospondin-1 antagonist of transforming growth factor-beta activation blocks cardiomyopathy in rats with diabetes and elevated angiotensin II.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Thrombospondin-1 is induced in rat myocardial infarction and its induction is accelerated by ischemia/reperfusion.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Alteration of thrombospondin-1 and -2 in rat brains following experimental intracerebral hemorrhage. Laboratory investigation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[A physiogenomic approach to study the regulation of blood pressure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of chloroquine on GFAP, PCNA and cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Apoptotic death of renal tubular cells in experimental sepsis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Suppression of haloperidol-induced oral dyskinesias in rats by vigabatrin.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Role of histamine H3 receptors during ischemia/reperfusion in isolated rat hearts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Renal and hepatic transporter expression in type 2 diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Down-regulation of intestinal drug transporters in chronic renal failure in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Modulation of gene expression by moxonidine in rats with chronic renal failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Estrogen receptor alpha supports cardiomyocytes indirectly through post-infarct cardiac c-kit+ cells.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Osteoprotegerin/RANK/RANKL axis in cardiac remodeling due to immuno-inflammatory myocardial disease.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Crystallin mRNA concentrations and distribution in lens of normal and galactosemic rats. Implications in development of sugar cataracts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Tuberin haploinsufficiency is associated with the loss of OGG1 in rat kidney tumors.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Heparan sulfate proteoglycan synthesis and its expression are decreased in the retina of diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein-associated O-GlcNAc.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression of the chemokine fractalkine (FKN/CX3CL1) by podocytes in normal and proteinuric rat kidney glomerulus.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in oxygen-induced lung injury in newborn rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Pax3 mRNA is decreased in the hearts of rats with experimental diaphragmatic hernia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[In vivo effect of surfactant on inflammatory cytokines during endotoxin-induced lung injury in rodents.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa: relevance of MKP-1, c-fos, c-myc, and cyclin D1 expression.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Visfatin: gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat: autoradiographic and functional evidence.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Down-regulation of cyclooxygenase-2 expression but up-regulation of cyclooxygenase-1 in renal carcinomas of the Eker (TSC2 gene mutant) rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Induction of heat shock proteins by hyperglycemic cerebral ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Proteomic analysis of rat heart in ischemia and ischemia-reperfusion using fluorescence two-dimensional difference gel electrophoresis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Subcellular stress response after traumatic brain injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Evaluation of molecular markers in a rat model of mammary carcinogenesis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[rAAV2-TGF-(3) decreases collagen synthesis and deposition in the liver of experimental hepatic fibrosis rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of human chorionic gonadotropin (hCG) and prolactin (PRL) on 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) expression and activity in the rat ovary.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Activation of matrix metalloproteinase-3 and agrin cleavage in cerebral ischemia/reperfusion.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Altered expression of goblet cell- and mucin glycosylation-related genes in the intestinal epithelium during infection with the nematode Nippostrongylus brasiliensis in rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inflammation- and ischemia-induced shedding of venular glycocalyx.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Region-specific plasticity in the epileptic rat brain: a hippocampal and extrahippocampal analysis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Spatial and temporal expression of CCR3 and the common beta chain of the IL-3, IL-5 and GM-CSF receptor in the nasal epithelium and lymphoid tissues in a rat model of allergic rhinitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Imaging E-selectin expression following traumatic brain injury in the rat using a targeted USPIO contrast agent.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Hippocampal Nogo-A and neo-Timm's staining in amygdala kindling rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Granulocyte colony-stimulating factor reduces cardiomyocyte apoptosis and improves cardiac function in adriamycin-induced cardiomyopathy in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Angiotensin type 1 receptor blockage improves ischemic injury following transient focal cerebral ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Enzymatic-nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The C-terminal region of S100A4 is important for its metastasis-inducing properties.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Plasminogen activator inhibitor type 1 up-regulation is associated with skeletal muscle atrophy and associated fibrosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Pax-6 is involved in the specification of hindbrain motor neuron subtype.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Downregulation of transforming growth factor-beta2 facilitates inflammation in the central nervous system by reciprocal astrocyte/microglia interactions.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Proteolysis of erythrocyte-type and brain-type ankyrins in rat heart after postischemic reperfusion.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Functional changes in rat-liver mitochondria during the early phase of burn injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[A germ-line insertion in the Birt-Hogg-Dub (BHD) gene gives rise to the Nihon rat model of inherited renal cancer.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of nitric oxide on Toll-like receptor 2/4 gene expression in the liver in acute hemorrhagic necrotizing pancreatitis in rats].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Differential effect of insulin treatment on decreased levels of beta-defensins and Toll-like receptors in diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhibition of the biosynthesis of uroporphyrinogen and heme in rat liver during obstructive jaundice produced by bile duct ligation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Imbalance between tissue inhibitor of metalloproteinase-4 and matrix metalloproteinases during acute myocardial [correction of myoctardial] ischemia-reperfusion injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Vigabatrin versus carbamazepine and phenytoin in kainic acid-treated pubescent rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Behavioral effects of vigabatrin correlated with whole brain gamma-aminobutyric acid metabolism in audiogenic sensitive rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The profile of cardiac cytochrome c oxidase (COX) expression in an accelerated cardiac-hypertrophy model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Apelin increases contractility in failing cardiac muscle.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD).]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Disparate regulation of signaling proteins after exercise and myocardial infarction.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Hepatic triacylglycerol lipase activities after induction of diabetes and administration of insulin or glucagon.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Induction of PDX-1-positive cells in the main duct during regeneration after acute necrotizing pancreatitis in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of mannoprotein E1 in liquid diet on inflammatory response and TLR5 expression in the gut of rats infected by Salmonella typhimurium.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Toll-like receptor 9 is expressed in rat pancreas and is involved in cerulein-induced pancreatitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of insulin treatment without and with recurrent hypoglycemia on hypoglycemic counterregulation and adrenal catecholamine-synthesizing enzymes in diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Selective losses of brainstem catecholamine neurons after hypoxia-ischemia in the immature rat pup.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhibition of ALK5 signaling induces physeal dysplasia in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro-hemorrhagic pancreatitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of vitamin E and human placenta cysteine peptidase inhibitor on expression of cathepsins B and L in implanted hepatoma Morris 5123 tumor model in Wistar rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The role of kinin B1 in the plasma extravasation of carrageenin-induced pleurisy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Oral administration of leflunomide (HWA486) results in prominent suppression of immunoglobulin E formation in a rat type 1 allergy model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a COX-2 inhibitor.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Pathophysiology of motility dysfunction in bowel obstruction: role of stretch-induced COX-2.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Leukaemia inhibitory factor is over-expressed by ischaemic brain tissue concomitant with reduced plasma expression following acute stroke.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Studies of ATP-sensitive potassium channels on 6-hydroxydopamine and haloperidol rat models of Parkinson's disease: implications for treating Parkinson's disease?]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Rodent oocytes express an active adenylyl cyclase required for meiotic arrest.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Differential expression of cytokines in the rat heart in response to sustained volume overload.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Identification of an apoptotic cleavage product of BARD1 as an autoantigen: a potential factor in the antitumoral response mediated by apoptotic bodies.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of omeprazole-induced achlorhydria on trefoil peptide expression in the rat stomach.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Beneficial effects of TLR-2/6 ligation in pulmonary bacterial infection and immunization with Pseudomonas aeruginosa.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Imidazoline receptors in the heart: characterization, distribution, and regulation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Excision repair cross-complementing 1 expression protects against ischemic injury following middle cerebral artery occlusion in the rat brain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Long-term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischemia and reperfusion in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Altered expression of calreticulin during the development of fibrosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression of aquaporin 1 and 4 in a congenital hydrocephalus rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Temporal changes in expression of aquaporin-3, -4, -5 and -8 in rat brains after permanent focal cerebral ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Changes of VEGF and AQPs gene and protein expression in rat brain tissue during hypoxic encephaledema].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Changes in ocular aquaporin-4 (AQP4) expression following retinal injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Changes in ocular aquaporin expression following optic nerve crush.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Kainate-induced seizures alter protein composition and N-methyl-D-aspartate receptor function of rat forebrain postsynaptic densities.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Regional expression of the hypoxia-inducible factor (HIF) system and association with cardiomyocyte cell cycle re-entry after myocardial infarction in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Aquaporin expression in blood-retinal barrier cells during experimental autoimmune uveitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[mRNA for NGF and p75 in the central nervous system of rats affected by experimental allergic encephalomyelitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Evaluation of nitric oxide (NO) and nitric oxide synthases (NOS) in the amniotic fluid in an experimental gastroschisis rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Influence of DMT1 and iron status on inflammatory responses in the lung.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The serine protease Omi/HtrA2 is involved in XIAP cleavage and in neuronal cell death following focal cerebral ischemia/reperfusion.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Alpha1-adrenoceptors involvement in painful diabetic neuropathy: a role in allodynia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Tanshinone IIA prevented brain iron dyshomeostasis in cerebral ischemic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhibition of mineralocorticoid receptor is a renoprotective effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Preclinical characterization of BRL 44408: antidepressant- and analgesic-like activity through selective alpha2A-adrenoceptor antagonism.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Gestational hypoxia alone or combined with restraint sensitizes the hypothalamic-pituitary-adrenal axis and induces anxiety-like behavior in adult male rat offspring.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The alterations of oligodendrocyte, myelin in corpus callosum, and cognitive dysfunction following chronic cerebral ischemia in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Association of increased S100B, S100A6 and S100P in serum levels with acute coronary syndrome and also with the severity of myocardial infarction in cardiac tissue of rat models with ischemia-reperfusion injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Presence of nerve growth factor and TrkA expression in the SVZ of EAE rats: evidence for a possible functional significance.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Increased cerebrospinal fluid levels of S100B protein in rat model of mania induced by ouabain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Long-term cognitive impairment and myelination deficiency in a rat model of perinatal hypoxic-ischemic brain injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced pain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Astrocytes are an early target in osmotic demyelination syndrome.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1beta in skeletal muscle.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Type I diabetes leads to tissue-specific DNA hypomethylation in male rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Aging and a peripheral immune challenge interact to reduce mature brain-derived neurotrophic factor and activation of TrkB, PLCgamma1, and ERK in hippocampal synaptoneurosomes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Proteome expression and carbonylation changes during Trypanosoma cruzi infection and Chagas disease in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Protective effect of lycopene on oxidative stress and cognitive decline in rotenone induced model of Parkinson's disease.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Overexpression of the gap junction protein Cx43 as found in diabetic foot ulcers can retard fibroblast migration.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effects of intravitreal triamcinolone acetonide on retinal gene expression in a rat model of central retinal vein occlusion.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Mesenteric adipose tissue alterations resulting from experimental reactivated colitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide-induced inflammatory cystitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[IL-2 and IFN-gamma in the retina of diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Differential gene expression pattern of diabetic rat retinas after intravitreal injection of erythropoietin.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Protein kinase C modulates the pulmonary inflammatory response in acute pancreatitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[An in-vivo analysis of capillary stasis and endothelial apoptosis in a model of hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Expression of gamma-aminobutyric acid A receptor subunits alpha1, beta1, gamma2 mRNA in rats with hepatic encephalopathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[An agonistic TrkB mAb causes sustained TrkB activation, delays RGC death, and protects the retinal structure in optic nerve axotomy and in glaucoma.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[T-tubule remodeling during transition from hypertrophy to heart failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Desipramine modulation of alpha-, gamma-synuclein, and the norepinephrine transporter in an animal model of depression.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Discordant expression of c-Ret and glial cell line-derived neurotrophic factor receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Autoimmune encephalomyelitis and uveitis induced by T cell immunity to self beta-synuclein.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Intracerebroventricular administration of quinolinic acid induces a selective decrease of inositol(1,4,5)-trisphosphate receptor in rat brain.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Irreversible aggregation of protein synthesis machinery after focal brain ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The signal transduction pathways involved in hepatic cytochrome P450 regulation in the rat during a lipopolysaccharide-induced model of central nervous system inflammation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Cooperation of the inducible nitric oxide synthase and cytochrome P450 1A1 in mediating lung inflammation and mutagenicity induced by diesel exhaust particles.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Induction of Hsp27 and Hsp32 stress proteins and vimentin in glial cells of the rat hippocampus following hyperthermia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Vimentin-immunopositive cells in the rat telencephalon after experimental ischemic stroke.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[In vivo anticoagulant effect of ethyl pyruvate in endotoxemic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Down-regulation of glial fibrillary acidic protein and vimentin by RNA interference improves acute urinary dysfunction associated with spinal cord injury in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Reduced CGP12177 binding to cardiac -adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Activation of JAK2/STAT pathway in cerebral cortex after experimental traumatic brain injury of rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Differential patterns of local gene regulation in crush lesions of the rat optic and sciatic nerve: relevance to posttraumatic regeneration.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Effect of inhalation of aerosolized unfractioned heparin on peri alveolar coagulability and inflammatory response in endotoxin induced acute lung injury rat model].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[The role and mechanism of the up-regulation of fibrinolytic activity in painful peripheral nerve injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

[Altered expression of metallothionein-I and -II and their receptor megalin in inherited photoreceptor degeneration.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[A model of experimental acute hematogenous pyelonephritis in the rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Upregulation of IRS-1 expression in Goto-Kakizaki rats following Roux-en-Y gastric bypass surgery: resolution of type 2 diabetes?]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Resveratrol inhibits neointimal formation after arterial injury through an endothelial nitric oxide synthase-dependent mechanism.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Upregulation of CSPG3 accompanies neuronal progenitor proliferation and migration in EAE.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The metabolic cascade leading to eicosanoid precursors--desaturases, elongases, and phospholipases A2--is altered in Zucker fatty rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Morphologic and biochemical characterization of brain injury in a model of controlled blast overpressure exposure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Hypoxia-inducible factor-1 (HIF-1) and autophagy in polycystic kidney disease (PKD).]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Role of inducible nitric oxide synthase pathway on methotrexate-induced intestinal mucositis in rodents.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Role of prostaglandin E2 in the synthesis of the pro-inflammatory cytokine interleukin-6 in primary sensory neurons: an in vivo and in vitro study.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Up-regulation of Cks1 and Skp2 with TNF/NF-B signaling in chronic progressive nephropathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Brain genomics of intracerebral hemorrhage.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Studies on gene expression in calvaria and serum levels of insulin-like growth factor-I and bone Gla protein in the methimazole-induced congenital hypothyroid rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The effect of Na(+)/H(+) exchanger-1 inhibition by sabiporide on blood-brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Stem cell therapy for arterial restenosis: potential parameters contributing to the success of bone marrow-derived mesenchymal stromal cells.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Interleukin-18 attenuates disruption of brain-blood barrier induced by status epilepticus within the rat piriform cortex in interferon- independent pathway.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The role of the dopamine D2 receptor in descending control of pain induced by motor cortex stimulation in the neuropathic rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Stress-induced depressive behaviors are correlated with Par-4 and DRD2 expression in rat striatum.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Candesartan cilexetil improves angiotensin II type 2 receptor-mediated neurite outgrowth via the PI3K-Akt pathway in fructose-induced insulin-resistant rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Folate-mediated incorporation of ring-2-carbon of histidine into nucleic acids: influence of thyroid hormone.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Long-term treatment with the apolipoprotein A1 mimetic peptide increases antioxidants and vascular repair in type I diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[STAT expression and localization in the central nervous system during autoimmune encephalomyelitis in Lewis rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[MyD88 signaling pathway is involved in renal fibrosis by favoring a TH2 immune response and activating alternative M2 macrophages.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of Ca2+ signalling in young type 2 Zucker diabetic fatty rat heart.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2, FKBP12.6, and SERCA2a in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Meta-analysis of genome-wide gene expression differences in onset and maintenance phases of genetic hypertension.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Akebia Saponin D attenuates amyloid -induced cognitive deficits and inflammatory response in rats: involvement of Akt/NF-B pathway.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Trigeminal-rostral ventromedial medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-B pathway.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Uncoupling protein downregulation in doxorubicin-induced heart failure improves mitochondrial coupling but increases reactive oxygen species generation.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The relationship between uncoupling protein 2 expression and myocardial high energy phosphates content in abdominal aorta constriction induced heart failure rats].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Tissue-specific alterations of methyl group metabolism with DNA hypermethylation in the Zucker (type 2) diabetic fatty rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Retention of fetuin-A in renal tubular lumen protects the kidney from nephrocalcinosis in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Evolution of matrix metalloprotease and tissue inhibitor expression during heart failure progression in the infarcted rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[ET(A)-receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Total glucosides of Danggui Buxue Tang attenuates bleomycin-induced pulmonary fibrosis via inhibition of extracellular matrix remodelling.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Cyclosporine-induced renal injury induces toll-like receptor and maturation of dendritic cells.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Target organ protection from a novel angiotensin II receptor (AT1) vaccine ATR12181 in spontaneously hypertensive rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Two novel vitamin D receptor modulators with similar structures exhibit different hypercalcemic effects in 5/6 nephrectomized uremic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Synergistic effect of malathion and estrogen on mammary gland carcinogenesis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effects of pulsed electromagnetic fields on bone mass and Wnt/-catenin signaling pathway in ovariectomized rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effects of periodontitis on aortic insulin resistance in an obese rat model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1alpha; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effects of acupoint-embedment of medicated-thread and acupoint-injection on expression of cortical urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in rats with cerebral ischemia-reperfusion injury].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Sex differences in the effect of high-fat diet feeding on rat white adipose tissue mitochondrial function and insulin sensitivity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Since increasing plasma apolipoprotein A-I (apoA-I) and HDL may reduce the complications of sepsis, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats undergoing cecal ligation and puncture (CLP) injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Isoflurane preconditioning confers cardioprotection by activation of ALDH2.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effects of interleukin 1 receptor antagonist on allergy asthma in rat model and its mechanism].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Expression of signal transducer and activator of transcription 6 in rat asthma model and the modulatory effect of dexamethasone].]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Morpho-mechanical intestinal remodeling in type 2 diabetic GK rats--is it related to advanced glycation end product formation?]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Mapping the time-dependent effects of paricalcitol on serum calcium, phosphorus and parathyroid hormone levels in 5/6 nephrectomized uremic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[KMUP-1 ameliorates monocrotaline-induced pulmonary arterial hypertension through the modulation of Ca2+ sensitization and K+-channel.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Submaximal suppression of parathyroid hormone ameliorates calcitriol-induced aortic calcification and remodeling and myocardial fibrosis in uremic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Neuroprotective effect of resveratrol on ischemia/reperfusion injury in rats through TRPC6/CREB pathways.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Effect of tangweian jianji on upper gastrointestinal remodeling in streptozotocin-induced diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Dynamic changes in HCN2, HCN4, KCNE1, and KCNE2 expression in ventricular cells from acute myocardial infarction rat hearts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[High-mobility-group box protein 1A box reduces development of sodium laurate-induced thromboangiitis obliterans in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Role of endogenous endothelin-1 in post-ischemic cardiac dysfunction and norepinephrine overflow in rat hearts.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Activation of VEGF and ERK1/2 and improvement of urethral function by adipose-derived stem cells in a rat stress urinary incontinence model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Expression of endothelin-1, endothelin-3, endothelin-converting enzyme-1, and endothelin-A and endothelin-B receptor mRNA after angioplasty-induced neointimal formation in the rat.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Increased expression of advanced glycation end-products and their receptor, and activation of nuclear factor kappa-B in lacrimal glands of diabetic rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Moxibustion treatment restoring the intestinal epithelium barrier in rats with Crohn's disease by down-regulating tumor necrosis factor alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Enhanced expression of angiotensin II receptor subtypes and angiotensin converting enzyme in medroxyprogesterone-induced mouse mammary adenocarcinomas.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Expression profiling and identification of novel genes in hepatocellular carcinomas.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Modulations of cytochrome P450 expression in diabetic mice by berberine.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The role of metallothionein in the pathogenesis of acute lung injury.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced prostate carcinogenesis in CYP1A-humanized mice.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Quantitative proteomics of a presymptomatic A53T alpha-synuclein Drosophila model of Parkinson disease.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Contribution of down-regulation of intestinal and hepatic cytochrome P450 3A to increased absorption of cyclosporine A in a rat nephrosis model.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Hepatic expression of cytochrome P450 in type 2 diabetic Goto-Kakizaki rats.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Blood gene expression markers to detect and distinguish target organ toxicity.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[HLA-A, -B, -DRB1 alleles and haplotypes frequencies in Moroccan patients with leukemia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
Gene-disease associations inferred from text-mining the literature.
DisGeNET evidence - LITERATURE
[Determination of HLA-A, -B allele polymorphism in the Luoba nationality living in Tibet Autonomous Region in China.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Polymorphism research on the distribution of four HLA alleles in five Chinese populations.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Association of HLA class I alleles with aloplecia areata in Chinese Hans.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The aim of the present study was to analyze the distribution of HLA-A, -B, -Cw, and -DRB1 alleles among patients with psoriatic arthritis (PsA) in Croatia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[These data add support to the genetic association of HLA class I and II with sarcoidosis in terms of susceptibility, type of presentation, severity and outcome.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Impact of select immunologic and virologic biomarkers on CD4 cell count decrease in patients with chronic HIV-1 subtype C infection: results from Sinikithemba Cohort, Durban, South Africa.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[In the whole, using PCR-based genotyping methods for HLA class I and class II loci, this study allows a preliminary description of HLA allele distribution in this Caribbean island and gives new elements which may be helpful in the anthropologic field as well as in HLA and disease association studies.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Our data are consistent with the Mestizo character of this population. In terms of genetic distance Peruvians are closest to Bolivians, which is in agreement with the geographical location and the cultural and anthropological background of the two human groups. Several HLA-B alleles originally described in genetically isolated Amerindian tribes are also present in the sample studied here. This fact and the reported finding of these alleles in several Amerindian groups suggests that they were present in the first wave of humans that populated South America (Paleoindians) before they split to give rise to the different South American tribes.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[We conclude that mutations of the HKII gene are not a major etiological factor for NIDDM in the Finnish population.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[ Although there is no significant difference of genotype distribution between ESCC patients and healthy controls, genotype C/T is associated with larger tumor and higher rate of lymph node metastasis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Polymorphism in the hypoxia-inducible factor 1alpha gene may confer susceptibility to androgen-independent prostate cancer.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[These results provide substantial evidence that genetic variation within or extremely close to IDE impacts both disease risk and traits related to the severity of AD.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[ These results demonstrate the biological significance of u-PA up-regulation in response to HGF in highly metastatic hormone refractory CaP cells.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Genetic approaches to the investigation of rheumatoid arthritis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[MPO genotype GG is associated with cirrhosis in patients with hereditary hemochromatosis.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Genes related to iron metabolism and susceptibility to Alzheimer's disease in Basque population.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Association between the HFE mutations and unsuccessful ageing: a study in Alzheimer's disease patients from Northern Italy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Our data suggest that variants of the hemochromatosis-transferrin receptor system have no direct effect on the incidence of breast cancer in Germany. Possible effects on tumor progression and prognosis remain elusive.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[ The conclusion is drawn that this mutation may be correlated to various rheumatic diseases.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[In conclusion, we failed to demonstrate that the C282Y and H63D HFE gene mutations were risk factors for CAD in Caucasians with type 2 diabetes lasting longer than 10 years.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[there were no significant differences in genotypes of H63D and C282Y between the case and control subjects.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Polymorphism of the HFE gene associated with hereditary hemochromatosis in populations of Russia.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Hemochromatosis gene variants in patients with cardiomyopathy.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[The authors examined whether the baseline cognitive functioning of 21 clinically normal huntingtin mutation carriers who developed manifest Huntington's disease on follow-up differed from that of 49 mutation carriers who remain asymptomatic over the same period in a longitudinal study.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
[ Our preliminary data suggest that mutation carriers might have an increased susceptibility to polydipsia through an undetermined mechanism.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine.
androgens results in increased nuclear levels of active SREBP
tscript(complex(SCOMP:"Nfkb Complex")) -> p(HGNC:IL6)
Protein I/II-mediated IL-6 and IL-8 secretion in human FLSs was inhibited by 90% by curcumin and sulphasalazine (which inhibit NFKB activation by blocking a signal leading to IKK activity), indicating that IL-6 and IL-8 activation is mediated through NFKB. Protein I/II-mediated IL-6 and IL-8 secretion by human Fibroblast-like synoviocytes was also inhibited 90% by peptide L-6-L (a selective inhibitor of NFKB).
gtp(p(HGNC:RAC2)) -> bp(GOBP:"cell proliferation")
In Rac2(-/-) T cells, proliferation was reduced upon stimulation with either plate-bound anti-CD3 or T cell receptor-specific antigen. This defect is accompanied with decreased activation of mitogen activated protein kinase extracellular signal-regulated kinase (ERK)1/2 and p38, and reduced Ca(2)+ mobilization. TCR stimulation-induced actin polymerization is also reduced
The phenotypic similarity of Rac2(-/-) to Vav(-/-) cells implicates Rac2 as a downstream mediator of Vav signaling
recombinant IL-6 to IL-6 KO animals before LPS or TNF-alpha challenge, replenished ANXA1 liver synthesis to that of WT animals.
In addition, we showed that overexpressing TTF-1 activates the endogenous rat nestin gene transcription.
cat(p(HGNC:FAS)) => complex(p(HGNC:FADD),p(HGNC:FAS),p(HGNC:CASP8))
Stimulation of CD95 leads to oligomerization of this receptor and the recruitment of the Fas-associated death domain (FADD) and procaspase-8 to form the death-inducing signaling complex (DISC)
gtp(p(SFAM:"RAS Family")) -| p(HGNC:PAWR)
On the other hand, prostate cancer cells LNCaP or normal prostatic epithelial cells that were resistant to apoptosis by Par-4 did not show Fas or FasL trafficking. Par-4 is down-regulated by oncogenic-Ras, -Raf, or -Src.
Par-4 induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway.
p(HGNC:CABLES1) -| bp(GOBP:"cell growth")
Expression of Cables in HeLa cells inhibited cell growth and colony formation
p(HGNC:PEBP1) -| (p(HGNC:TNF) -> tscript(complex(SCOMP:"Nfkb Complex")))
p(HGNC:TNF) -> tscript(complex(SCOMP:"Nfkb Complex"))
We show here that RKIP also antagonizes the signal transduction pathways that mediate the activation of the transcription factor nuclear factor kappa B (NF-kappaB) in response to stimulation with tumor necrosis factor alpha (TNF-alpha) or interleukin 1 beta.
After 28 days of cafeteria diet, the level of the mRNA of PPAR alpha and acyl-CoA oxidase (ACOX) was significantly increased (+54.5% and +37.8%, P <.01 and P <.05, respectively)...
tscript(p(HGNC:ETS2)) => tscript(p(HGNC:SMAD3))
Addition of Ets1 greatly enhanced the Smad3/TGF beta-mediated activation. Ets2 had also some effect, whereas other Ets proteins, Elf-1, Ese-1, and Erf-1, failed to cooperate with Smad3.
tscript(p(HGNC:ETS1)) -> tscript(p(HGNC:SMAD4))
Smad3 and Smad4 were able to specifically interact with the PTHrP P3-AGAC box and to bind to the P3 promoter together with Ets1. Inhibition of endogenous Ets1 expression by calphostin C abrogated TGF beta-induced up-regulation of the P3 transcript, whereas it did not affect the TGF beta effect on PAI expression.
a(CHEBI:"25-hydroxycholesterol") -| r(HGNC:SREBF2)
Factor-dependent cell progenitor promyeloid cells expressed functional IL-10Rs, as assessed by precipitation of a 110-kDa protein with an Ab to the IL-10R and by the ability of IL-10 to activate Jak1 and Tyk2 and to phosphorylate tyrosine 705 on Stat-3.
cat(p(MGI:Il10ra)) -| bp(MESHPP:Apoptosis)
Here we show that IL-10 directly affects progenitor myeloid cells by protecting them from death following the removal of growth factors.
This survival-promoting activity is totally due to IL-10 stimulating the insulin receptor substrate-2/PI 3-kinase/Akt pathway, which increases the anti-apoptotic activity of ERK1/2.
bp(GOBP:"hypotonic response") -> r(RGD:Clu)
As shown by Northern blot analysis, PRTB and clusterin mRNA levels were upregulated by 19-64% after 4-8 h by both ammonia and hypoosmolarity.
bp(GOBP:"response to osmotic stress") -> r(RGD:Dazap2)
gtp(p(SFAM:"RAS Family")) -> path(SDIS:"Oncogene induced senescence")
senescence was induced by replicative exhaustion, oncogenic RAS, p14(ARF), or hydrogen peroxide
kin(p(HGNC:LYN)) => p(HGNC:NMT1,pmod(P,Y,180))
a(SCHEM:"SM 11044") -> cat(p(HGNC:ADRB1))
SM-11044, a nonselective beta-adrenoreceptor agonist
a(SCHEM:"SM 11044") -> cat(p(HGNC:ADRB3))
SERCA2 promoter induction by calcium depletion was partially blocked by dominant-negative ATF6, whereas constitutively activated ATF6 led to SERCA2 promoter activation
path(SDIS:"laminar shear stress") -| r(HGNC:ADSS)
Table 1. Differential gene expression in HAECs in response to 24-h shear stress - laminar shear stress at 12 dyn/cm(2)
path(SDIS:"laminar shear stress") -| r(HGNC:CCL25)
path(SDIS:"laminar shear stress") -| r(HGNC:COL2A1)
path(SDIS:"laminar shear stress") -| r(HGNC:DVL1)
path(SDIS:"laminar shear stress") -| r(HGNC:ISG20)
path(SDIS:"laminar shear stress") -| r(HGNC:LAMA4)
path(SDIS:"laminar shear stress") -| r(HGNC:LFNG)
path(SDIS:"laminar shear stress") -| r(HGNC:NUP153)
path(SDIS:"laminar shear stress") -| r(HGNC:PPAT)
path(SDIS:"laminar shear stress") -| r(HGNC:PTBP1)
path(SDIS:"laminar shear stress") -| r(HGNC:TNFSF8)
path(SDIS:"laminar shear stress") -| r(HGNC:UMPS)
path(SDIS:"laminar shear stress") -> r(HGNC:ATP5J)
path(SDIS:"laminar shear stress") -> r(HGNC:ANGPT2)
path(SDIS:"laminar shear stress") -> r(HGNC:IKZF1)
path(SDIS:"laminar shear stress") -> r(HGNC:ILK)
path(SDIS:"laminar shear stress") -> r(HGNC:MAPK10)
path(SDIS:"laminar shear stress") -> r(HGNC:TUBG1)
path(SDIS:"laminar shear stress") -> r(HGNC:VIM)
In contrast, TNF-alpha activation of the IL-8 promoter was mediated almost entirely through the nuclear factor-?B and activation protein-1 response elements present between -70 and -133 bp of the IL-8 promoter.
kin(p(SFAM:"AKT Family")) -> r(HGNC:MSR1)
We also demonstrated that the constitutively active form of Akt enhanced activity of the SRA promoter but that the dominant-negative mutant of Akt completely abolished the expression of SRA after treatment with Gas6.
In the present study we report for the first time that plasma LTIP (activity and mass) is increased 3-fold above control levels in individuals with elevated cholesterol
a(CHEBI:troglitazone) -| kin(p(RGD:Prkcd))
PPARgamma ligands regulate p21(Cip1) at a post-translational level by blocking PKCdelta signaling and accelerating p21(Cip1) turnover.
a(CHEBI:troglitazone) -| (p(SFAM:"PDGF Family") -> p(RGD:Cdkn1a))
PPARgamma ligands troglitazone (TRO, 10 microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1) protein by platelet-derived growth factor (PDGF) and insulin without affecting cognate mRNA levels in rat aortic smooth muscle cells (RASMC).
a(CHEBI:wortmannin) -| kin(p(HGNC:AKT1))
the sensitivity of insulin-stimulated activation of PKC zeta/lambda, Akt1, Akt2 and Akt3 to wortmannin correlated closely with inhibition of GLUT4 translocation
a(SCHEM:"serum insulin") -> path(SDIS:"muscle glucose import")
wortmannin inhibited insulin-stimulated glucose uptake
Here we report a novel signaling pathway whereby RhoA can efficiently modulate Stat3 transcriptional activity by inducing its simultaneous tyrosine and serine phosphorylation. Tyrosine phosphorylation is exerted via a member of the Src family of kinases (SrcFK) and JAK2, whereas the JNK pathway mediates serine phosphorylation.
gtp(p(HGNC:RHOA)) -> tscript(p(HGNC:STAT3))
a(SCHEM:Tretinoin) -| bp(GOBP:"cell proliferation")
Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells.
TREM-2 Triggers Rapid Upregulation of CCR7 and Increased Expression of MHC Class II, CD86, and CD40.
kin(p(RGD:Insr)) => p(RGD:Khdrbs1,pmod(P,Y))
The 68 kDa Src substrate associated during mitosis (Sam68) is an RNA binding protein with Src homology (SH) 2 and 3 domain binding sites. We have recently found that Sam68 is a substrate of the insulin receptor (IR) and that Tyr-phosphorylated Sam68 associates with the SH2 domains of p85 PI3K. In the present work, using HTC-IR cells, we have found that insulin stimulation promotes the relocalization of Sam68 from the nucleus to the cytoplasm, and we have further studied the role of Sam68 in insulin receptor signaling complexes, by co-precipitating experiments. Thus, Sam68 is co-precipitated with p85 PI3K, IRS-1 and IR. The association of Sam68 with these complexes is mediated by the SH2 domains of PI3K. Moreover, we have found that Sam68 is a p120GAP associated protein after Tyr-phosphorylation by the IR. This association is mediated by the SH2 domains of GAP (preferentially the C-terminal SH2). Thus, Sam68 is linking p120GAP to PI3K signaling pathway. In fact, PI3K activity was increased in both anti-Sam68 and anti-GAP immmunoprecipitates upon insulin stimulation. We propose that the recruitment of the docking protein Sam68 to the PI3K pathway may serve to allow the association of other signaling molecules, i.e. p120GAP. In this way, these signaling complexes may modulate other signaling cascades of IR, such as p21Ras pathway.
kin(p(HGNC:MAPK14)) => p(HGNC:SLC9A1,pmod(P,S,726))
growth of the primary melanoma cell lines was stimulated by TIMP-1 and inhibited by TIMP-2.
bp(GOBP:"response to radiation") -> r(HGNC:DFFB)
The protein microarray approach revealed radiation-induced up-regulation of apoptotic regulators including p53, DNA fragmentation factor 40/caspase activated DNase, DNA fragmentation factor 45/inhibitor of caspase activated DNase, tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5, decoy receptor 2, FLICE-like inhibitory protein, signal transducers and activators of transcription 1alpha, and uncoupling protein 2
bp(GOBP:"response to radiation") -> r(HGNC:STAT1)
Ariadne: Western immunoblots further revealed that Ang II (100 n M ; 1...24 h) increased neuronal MIF protein expression. incubation of cultures with Ang II (100 nM; 1-24 h) elicited an increase in MIF gene expression.
LDL, in pathophysiological concentrations, affect the IGF-I signaling pathway at multiple levels: 1) they induce phosphorylation of IGF-I receptor beta and IRS-1 in a time- and dose-dependent manner; 2) they up-regulate IRS-1-associated PI3 kinase/Akt activation in response to IGF-I at early times; and 3) they show additive effects with IGF-I on extracellular signal-regulated MAPK 1/2 phosphorylation.
a(SCHEM:"Low Density Lipoprotein") -> (p(HGNC:IGF1) -> p(HGNC:IGF1R,pmod(P,Y)))
Although the expression of calsequestrin, triadin, and phospholamban was not altered, we observed a progressive decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic receptors
Co-transfection of HSP 40 with 120Q dramatically inhibited the formation of huntingtin aggregates (Fig. 2 A ).
Exogenously added IFN-alpha upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines.
a(SCHEM:"Oxidized Low Density Lipoprotein") -| cat(p(HGNC:PON1))
cat(p(HGNC:ADRB2)) -> path(SDIS:"adipocyte lipolysis")
We investigated the mechanisms responsible for the anti-lipolytic effect of intracellular Ca2+ ([Ca2+]i) in human adipocytes. Increasing [Ca2+]i inhibited lipolysis induced by b-adrenergic receptor activation, A1 adenosine receptor inhibition, adenylate cyclase activation, and phosphodiesterase (PDE) inhibition, as well as by a hydrolyzable cAMP analog,
These results demonstrate that arsenite-induced VEGF mRNA and HIF-1alpha protein expression is independent of increased ROS production but critically regulated by the cellular reduced glutathione content. In addition, these data suggest the involvement of a thiol-sensitive mechanism in the regulation of VEGF mRNA expression and HIF-1alpha protein in human ovarian cancer cells.
We found that the Jagged1 (JAG1) and Jagged2 (JAG2) genes, encoding ligands for the Notch receptors, are up-regulated by p63 and p73.
a(CHEBI:histamine) -> kin(p(HGNC:ADRBK2))
GRK2 and GRK3 were the most potent in augmenting desensitization
Here, we have identified EphA2 as a target gene of the p53 family, that is, p53, p73, and p63. We found that EphA2 expression resulted in an increase in apoptosis
p(HGNC:CSF2) -> complex(p(HGNC:ADRBK2),p(HGNC:CXCR4))
Cytokine treatment also increased the total and tyrosine-specific phosphorylation of CXCR4 as well as the phosphorylation of FAK on tyrosine 397. It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes.
and up-regulated by IL-10 and transforming growth factor-beta 1. Down-regulation was mediated post-translationally, in the absence of protein degradation, through an endocytotic mechanism.
surf(p(HGNC:CXCR4)) -> cat(p(HGNC:CXCR4))
surface CXCR4 expression was down-regulated by cytokines interleukin-4 (IL-4), IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
On the other hand, CCL2, CCL5, and CXCL12 were expressed on RA FLS, and their production was regulated by TNF-alpha, IL-1beta, and TGF-beta1.
Treatment of fibroblast-like synoviocyte (FLS) cultures with RS-504393, a CCR-2 antagonist significantly inhibited the CCL-2 induced ERK-2 activation, indicating that CCL-2 induced ERK-2 activation was mediated by CCR-2.
cat(p(HGNC:IL6R)) -> tscript(p(HGNC:STAT3))
DNA fragments corresponding to the two upstream hypersensitive sites of both genes have enhancer activity that depends upon the liver-enriched transcription factor binding sites for hepatocyte nuclear factor (HNF) 1 and/or CCAAT/enhancer binding protein (C/EBP).
The expression of the LDL receptor was also increased by insulin treatment, as described previously in diabetic rats injected with insulin ( 5 ).
Mutations in hepatocyte nuclear factor 1 alpha (HNF-1A) lead to maturity-onset diabetes of the young type 3 as a result of impaired insulin secretory response in pancreatic Beta-cells. Furthermore the expression of steady-state mRNA levels of gene encoding glucose transporter 2 (Glut2) was found to be decreased in Hnf-1-/- adult and new born mice, suggesting that HNF-1 alpha leads to the expression of GLUT-2 in pancreatic islets of mice.
bp(GOBP:"response to hypoxia") -> p(RGD:Il10)
p(RGD:Tnf) -> (bp(GOBP:"response to hypoxia") -> p(RGD:Il10))
Rolipram had little effect on the increases of IL-1 beta concentrations in lung and serum, whereas treatment with anti-TNF-alpha markedly increased the concentration of this cytokine. Concentrations of IL-10 rose significantly in the lung and serum and these increases were blocked by rolipram or anti-TNF-alpha.
p(MGI:Prkcz) -| bp(GOBP:"cell migration")
PKCzeta down-regulation is shown to be a critical determinant of cell migration. Transfection of high-motility cells with either wild-type PKCzeta or its regulatory domain suppresses migration.
kin(p(RGD:Jak2)) -> tscript(p(RGD:Stat5a))
However, using an antibody that recognizes the tyrosine-phosphorylated forms of both Stat5a and Stat5b (Y694/Y699), it was found that AG490 could inhibit PRL-induced Stat5a phosphorylation only and had little or no effect on Stat5b phosphorylation.
their expression is up-regulated by the activation of leukemia inhibitory factor receptor (LIF-R) and prostacyclin receptor (IP-R) via the extracellular signal-regulated kinase (ERK) pathway and cAMP production, respectively.
cat(p(HGNC:PTGIR)) -> kin(p(HGNC:MAPK1))
p(HGNC:CREBBP) => tscript(p(HGNC:NFE2L2))
Nrf2 contains two transcription activation domains, Neh4 and Neh5, which act synergistically to attain maximum a activation of reporter gene expression. Neh4 and Neh5 both individually and cooperatively bind to CBP
complex(p(MGI:Cebpb),p(MGI:Casp8)) -| cat(p(MGI:Casp8))
C/EBPbeta-PThr(217) and the phosphorylation mimic C/EBPbeta-Glu(217), but not C/EBPbeta-Ala(217), were associated with procaspases 1 and 8 in vivo and in vitro and inhibited their activation.
kin(p(HGNC:CDK2)) -> bp(GOBP:"cell proliferation")
C/EBPalpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases
kin(p(HGNC:CDK4)) -> bp(GOBP:"cell proliferation")
tscript(p(HGNC:CEBPA)) -| kin(p(HGNC:CDK2))
tscript(p(HGNC:CEBPA)) -| bp(GOBP:"cell proliferation")
The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a strong inhibitor of cell proliferation
path(SDIS:Diabetes) positiveCorrelation p(HGNC:PRL)
Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, GH, and ferritin.
cat(p(HGNC:TRADD)) -> cat(p(HGNC:CASP8))
We also showed that overexpressed NH2 termini of K18 and K8/18 were associated with endogenous TRADD in SW13 cells, resulting in the inhibition of caspase-8 activation.
EGF-R causes disassembly of hemidesmosomes by activating Fyn, which in turn phosphorylates the beta4 cytoplasmic domain. Neoplastic cells expressing dominant negative Fyn display increased hemidesmosomes and migrate poorly in vitro in response to EGF.
In Hoxa9HF1 cells, Meis1a prevented G-CSF-induced transcriptional up-regulation of the genes encoding gp91phox (subunit of the respiratory burst oxidase), lactoferrin, Egr-1, neutrophil gelatinase B, and the lipopolysaccharide receptor (CD14), each of which is normally activated coincident with neutrophil differentiation (Fig. 1 J)
bp(GOBP:"response to hypoxia") -> r(HGNC:HK2)
hexokinase II and DEC1/Stra13, genes known to be hypoxia inducible in other systems, were found to be hypoxia inducible in our pancreatic cancer system.
p(HGNC:MAP3K5,pmod(P,T)) => kin(p(HGNC:MAP3K5))
A yeast two-hybrid screening identified a serine/threonine protein phosphatase 5 (PP5) as a binding partner of ASK1. PP5 directly dephosphorylated an essential phospho-threonine residue within the kinase domain of ASK1 and thereby inactivated ASK1 activity in vitro and in vivo
Smad3 and E2F-4 directly bound to the element (TIE/E2F) in the myc promoter
complex(p(MGI:Il6st),p(MGI:Hck)) -> bp(GOBP:"cell proliferation")
identification of an acidic domain of gp130 as a binding region for Hck, which mediates proliferative signaling the deletion of this region of gp130 resulted in a significant reduction of Hck kinase activity and cell proliferation upon stimulation of gp130 compared to wild-type gp130
this acidic domain of gp130 is responsible for the activation of Hck, Erk, Pyk2 and signals cell proliferation upon growth factor stimulation
a(CHEBI:"hydrogen peroxide") -> r(MGI:Dusp1)
kin(p(MGI:Mapk14)) -> (a(CHEBI:"hydrogen peroxide") -> r(MGI:Dusp1))
transcriptional induction of MKP-1, histone H3 modification, and elevation in MKP-1 mRNA in response to arsenite are all partially prevented by the p38 MAP kinase inhibitor SB203580
a(CHEBI:"trichostatin A") -> r(HGNC:PRKCDBP)
Treatment of breast cancer MCF7 cells with 5'azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation.
a(SCHEM:"PD 98,059") -| (p(HGNC:IL17A) -> p(HGNC:MAPK1,pmod(P,T)))
p(HGNC:IL17A) -> p(HGNC:MAPK1,pmod(P,T))
In addition, preincubation of the cells with an MEK inhibitor, PD98059 (10 ?mol/L), diminished the activation of ERK1/2 in PBECs, and preincubation with 0.1% DMSO did not affect the phosphorylation of ERK1/2 (Fig 2, B).
untreated or IL- 17–stimulated cells were lysed at various time points... Western blot analysis revealed the phosphorylation of ERK1/2 to reach a maximum at approximately 20 minutes and to return to baseline levels by 60 minutes (Fig 2, A).
cat(p(HGNC:CASP3)) -| (p(HGNC:PARP1) -| cat(p(HGNC:DNASE1L3)))
caspase-3 prevented the inhibition of DNAS1L3 endonuclease activity by wild-type PARP-1
Incubation of cells with TNF-alpha for various lengths of time up to 6 hours showed a maximum activation of p42/44 between 10 and 30 minutes after TNF-alpha treatment.