Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activation

Hdl Handle:
http://hdl.handle.net/10675.2/606
Title:
Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activation
Authors:
El-Remessy, Azza B. ( 0000-0003-4386-1989 ) ; Tawfik, Huda E.; Matragoon, Suraporn; Pillai, Bindu; Caldwell, Ruth B. ( 0000-0003-0168-0354 ) ; Caldwell, Robert William
Abstract:
Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15â mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.
Citation:
Exp Diabetes Res. 2010 Nov 1; 2010:247861
Issue Date:
1-Nov-2010
URI:
http://hdl.handle.net/10675.2/606
DOI:
10.1155/2010/247861
PubMed ID:
21052489
PubMed Central ID:
PMC2967829
Type:
Article
ISSN:
1687-5303
Appears in Collections:
Department of Pharmacology and Toxicology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorEl-Remessy, Azza B.en_US
dc.contributor.authorTawfik, Huda E.en_US
dc.contributor.authorMatragoon, Surapornen_US
dc.contributor.authorPillai, Binduen_US
dc.contributor.authorCaldwell, Ruth B.en_US
dc.contributor.authorCaldwell, Robert Williamen_US
dc.date.accessioned2012-10-26T16:26:51Z-
dc.date.available2012-10-26T16:26:51Z-
dc.date.issued2010-11-1en_US
dc.identifier.citationExp Diabetes Res. 2010 Nov 1; 2010:247861en_US
dc.identifier.issn1687-5303en_US
dc.identifier.pmid21052489en_US
dc.identifier.doi10.1155/2010/247861en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/606-
dc.description.abstractEndothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15â mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.en_US
dc.rightsCopyright © 2010 Azza B. El-Remessy et al.en_US
dc.subjectResearch Articleen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAortaen_US
dc.subject.meshBiological Markersen_US
dc.subject.meshCattleen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCoronary Vesselsen_US
dc.subject.meshDiabetic Angiopathiesen_US
dc.subject.meshEndothelium, Vascularen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshGene Expression Regulation, Enzymologicen_US
dc.subject.meshHyperglycemiaen_US
dc.subject.meshMaleen_US
dc.subject.meshMetalloporphyrinsen_US
dc.subject.meshNitric Oxide Synthase Type IIIen_US
dc.subject.meshOxidative Stressen_US
dc.subject.meshPeroxynitrous Aciden_US
dc.subject.meshProtein Kinase Inhibitorsen_US
dc.subject.meshRNA, Messengeren_US
dc.subject.meshRandom Allocationen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshVasodilationen_US
dc.subject.meshrho-Associated Kinasesen_US
dc.titlePeroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activationen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2967829en_US
dc.contributor.corporatenameDepartment of Pharmacology and Toxicology-
dc.contributor.corporatenameVascular Biology Center-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.