http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#Head http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#provenance http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#pubinfo http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_1 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=9606 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://www.ebi.ac.uk/chebi/searchId.do?chebiId=26523 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://resource.belframework.org/belframework/20131211/namespace/selventa-legacy-chemicals/serum%20glucose http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.w3.org/2000/01/rdf-schema#label a(SCHEM:"serum glucose") -> a(CHEBI:"reactive oxygen species") http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#provenance http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_3 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_2 http://www.w3.org/ns/prov#value We previously proposed that the production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development of diabetes complications. The association between the pathogenesis of diabetes and its complications and mitochondrial biogenesis has been recently reported. Because metformin has been reported to exert a possible additional benefit in preventing diabetes complications, we investigated the effect of metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on mtROS production and mitochondrial biogenesis in cultured human umbilical vein endothelial cells. Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs. The dominant negative form of AMPKalpha1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1alpha completely blocked the hyperglycemia-induced mtROS production. In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation. Dominant negative-AMPK also reduced the effects of metformin and AICAR on these observations. These results suggest that metformin normalizes hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis through the activation of AMPK-PGC-1alpha pathway. http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_2 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/16380484 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_3 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/16380484 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#_2 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0#pubinfo http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://purl.org/dc/terms/created 2014-07-03T14:32:54.546+02:00 http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAW0AtUWUvwO4GNUve_ieHDzrvP9T6vGv9oE69H0r-TV0 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234