Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954306 | Journal of Molecular and Cellular Cardiology | 2005 | 4 Pages |
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.
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Authors
Tohru Yamamori, Anthony R. White, Ilwola Mattagajasingh, Firdous A. Khanday, Azeb Haile, Bing Qi, Byeong Hwa Jeon, Artem Bugayenko, Kenji Kasuno, Dan E. Berkowitz, Kaikobad Irani,