Journal article
P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction
Journal of molecular and cellular cardiology, Vol.39(6), pp.992-995
2005
DOI: 10.1016/j.yjmcc.2005.09.003
PMID: 16242150
Abstract
The p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production. RNAi-mediated down-regulation of endogenous p66shc led to activation of the proto-oncogene ras, and Akt kinase, with a corresponding increase in phosphorylation of eNOS at S1177 (S1179 on bovine eNOS). In rat aortic rings, down-regulation of p66shc suppressed the vasoconstrictor response to phenyephrine that was abrogated by treatment with the NOS inhibitor
l-NAME, and enhanced vasodilation induced by sub-maximal doses of acetylcholine. These findings highlight a pivotal role for p66shc in inhibiting endothelial NO production, and endothelium-dependent vasorelaxation, that may provide important mechanistic information about endothelial dysfunction seen with aging.
Details
- Title: Subtitle
- P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction
- Creators
- Tohru Yamamori - Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife 620, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USAAnthony R White - Johns Hopkins University School of Medicine, Baltimore, MD, USAIlwola Mattagajasingh - Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife 620, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USAFirdous A Khanday - Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife 620, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USAAzeb Haile - Johns Hopkins University School of Medicine, Baltimore, MD, USABing Qi - Johns Hopkins University School of Medicine, Baltimore, MD, USAByeong Hwa Jeon - Chungnam National University, Taejeon, South KoreaArtem Bugayenko - Johns Hopkins University School of Medicine, Baltimore, MD, USAKenji Kasuno - Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife 620, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USADan E Berkowitz - Johns Hopkins University School of Medicine, Baltimore, MD, USAKaikobad Irani - Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife 620, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USA
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.39(6), pp.992-995
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.yjmcc.2005.09.003
- PMID
- 16242150
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Language
- English
- Date published
- 2005
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984046921102771
Metrics
10 Record Views