P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction

Academic Article


  • 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. © 2005 Elsevier Ltd. All rights reserved.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Yamamori T; White AR; Mattagajasingh I; Khanday FA; Haile A; Qi B; Byeong HJ; Bugayenko A; Kasuno K; Berkowitz DE
  • Start Page

  • 992
  • End Page

  • 995
  • Volume

  • 39
  • Issue

  • 6