Linked Life Data

14593122

Source:http://linkedlifedata.com/resource/pubmed/id/14593122

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-1-19
pubmed:abstractText
Recently, peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been reported to increase endothelial NO, but the signaling mechanisms involved are unknown. Using troglitazone, a PPARgamma ligand known as an antidiabetic compound, we investigated the molecular mechanism of its effect on NO production in bovine aortic endothelial cells. Troglitazone increased endothelial NO production in a dose- and time-dependent manner with no alteration in endothelial nitric-oxide synthase (eNOS) expression. The maximal increase ( approximately 3.1-fold) was achieved with 20 microm troglitazone treatment for 12 h, and this increase was accompanied by increases in the expression of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, and in Akt phosphorylation. Analysis with antibodies specific for each phosphorylated site demonstrated that troglitazone (20 microm treatment for 12 h) significantly increased both the phosphorylation of Ser(1179) of eNOS (eNOS-Ser(1179)) and the dephosphorylation of eNOS-Ser(116) but did not alter eNOS-Thr(497) phosphorylation. Treatment with anti-VEGF antibody to scavenge the increased VEGF induced by troglitazone partially inhibited troglitazone-stimulated NO production. This was accompanied by the attenuation of troglitazone-stimulated increases in the phosphorylation of Akt and eNOS-Ser(1179) with no alteration in eNOS-Ser(116) dephosphorylation. We also found that bisphenol A diglycidyl ether, a PPARgamma antagonist, partially inhibited troglitazone-stimulated NO production with a concomitant reduction in VEGF-KDR/Flk-1-Akt-mediated eNOS-Ser(1179) phosphorylation but with no alteration in eNOS-Ser(116) dephosphorylation induced by troglitazone. Taken together, our results demonstrate that prolonged treatment with troglitazone increases endothelial NO production by at least two independent signaling pathways: PPARgamma-dependent, VEGF-KDR/Flk-1-Akt-mediated eNOS-Ser(1179) phosphorylation and PPARgamma-independent, eNOS-Ser(116) dephosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2,2-bis(4-glycidyloxyphenyl)propane, http://linkedlifedata.com/resource/pubmed/chemical/Chromans, http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents, http://linkedlifedata.com/resource/pubmed/chemical/troglitazone
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2499-506
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Nitric oxide production and regulation of endothelial nitric-oxide synthase phosphorylation by prolonged treatment with troglitazone: evidence for involvement of peroxisome proliferator-activated receptor (PPAR) gamma-dependent and PPARgamma-independent signaling pathways.
pubmed:affiliation
Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-701, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't