@prefix this: <http://www.tkuhn.ch/bel2nanopub/RA_00_lOndPW67imglilj3hLcy5jzSCRanRTBbeT40Z_0> .
@prefix sub: <http://www.tkuhn.ch/bel2nanopub/RA_00_lOndPW67imglilj3hLcy5jzSCRanRTBbeT40Z_0#> .
@prefix beldoc: <http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix dce: <http://purl.org/dc/elements/1.1/> .
@prefix pav: <http://purl.org/pav/> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix belv: <http://www.selventa.com/vocabulary/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix Protein: <http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_36080> .
@prefix hgnc: <http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=> .
@prefix geneProductOf: <http://purl.obolibrary.org/obo/RO_0002204> .
@prefix go: <http://amigo.geneontology.org/amigo/term/GO:> .
@prefix scomp: <http://resource.belframework.org/belframework/20131211/namespace/selventa-named-complexes/> .
@prefix ProteinComplex: <http://amigo.geneontology.org/amigo/term/GO:0043234> .
@prefix hasAgent: <http://semanticscience.org/resource/SIO_000139> .
@prefix obo: <http://purl.obolibrary.org/obo/> .
@prefix occursIn: <http://purl.obolibrary.org/obo/BFO_0000066> .
@prefix species: <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=> .
@prefix pubmed: <http://www.ncbi.nlm.nih.gov/pubmed/> .
@prefix orcid: <http://orcid.org/> .

sub:Head {
  this: np:hasAssertion sub:assertion;
    np:hasProvenance sub:provenance;
    np:hasPublicationInfo sub:pubinfo;
    a np:Nanopublication .
}

sub:assertion {
  scomp:IkappaB%20Kinase%20Complex a ProteinComplex: .
  
  sub:_1 geneProductOf: hgnc:11892;
    a Protein: .
  
  sub:_2 hasAgent: scomp:IkappaB%20Kinase%20Complex;
    a go:0016301 .
  
  sub:_3 occursIn: obo:EFO_0002795, species:9606;
    rdf:object sub:_2;
    rdf:predicate belv:increases;
    rdf:subject sub:_1;
    a rdf:Statement .
  
  sub:assertion rdfs:label "p(HGNC:TNF) -> kin(complex(SCOMP:\"IkappaB Kinase Complex\"))" .
}

sub:provenance {
  beldoc: dce:description "Approximately 61,000 statements.";
    dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
    dce:title "BEL Framework Large Corpus Document";
    pav:authoredBy sub:_5;
    pav:version "20131211" .
  
  sub:_4 prov:value "AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in regulation of energy homeostasis and metabolic stress. Metformin has been shown to activate AMPK. We hypothesized that metformin may prevent nuclear factor kappaB (NF-kappaB) activation in endothelial cells exposed to inflammatory cytokines. Metformin was observed to activate AMPK, as well as its downstream target, phosphoacetyl coenzyme A carboxylase, in human umbilical vein endothelial cells (HUVECs). Metformin also dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF-alpha-induced IkappaB kinase activity. Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), dose-dependently inhibited TNF-alpha- and interleukin-1beta-induced NF-kappaB reporter gene expression. AICAR also suppressed the TNF-alpha- and interleukin-1beta-induced gene expression of vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 in HUVECs. The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation. In light of these findings, we suggest that metformin attenuates the cytokine-induced expression of proinflammatory and adhesion molecule genes by inhibiting NF-kappaB activation via AMPK activation. Thus, it might be useful to target AMPK signaling in future efforts to prevent atherogenic and inflammatory vascular disease.";
    prov:wasQuotedFrom pubmed:16636195 .
  
  sub:_5 rdfs:label "Selventa" .
  
  sub:assertion prov:hadPrimarySource pubmed:16636195;
    prov:wasDerivedFrom beldoc:, sub:_4 .
}

sub:pubinfo {
  this: dct:created "2014-07-03T14:33:00.036+02:00"^^xsd:dateTime;
    pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}