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

Tohru Yamamori; Anthony R. White; Ilwola Mattagajasingh; Firdous A. Khanday; Azeb Haile; Bing Qi; Hwa Jeon Byeong; Artem Bugayenko; Kenji Kasuno; Dan E. Berkowitz; Kaikobad Irani

doi:10.1016/j.yjmcc.2005.09.003

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

Tohru Yamamori, Anthony R. White, Ilwola Mattagajasingh, Firdous A. Khanday, Azeb Haile, Bing Qi, Hwa Jeon Byeong, Artem Bugayenko, Kenji Kasuno, Dan E. Berkowitz, Kaikobad Irani

School of Medicine

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

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.

Original language	English (US)
Pages (from-to)	992-995
Number of pages	4
Journal	Journal of Molecular and Cellular Cardiology
Volume	39
Issue number	6
DOIs	https://doi.org/10.1016/j.yjmcc.2005.09.003
State	Published - Dec 2005

Keywords

Endothelium
Nitric oxide
P66shc
Ras
Vascular tone

ASJC Scopus subject areas

Molecular Biology
Cardiology and Cardiovascular Medicine

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10.1016/j.yjmcc.2005.09.003

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Yamamori, T., White, A. R., Mattagajasingh, I., Khanday, F. A., Haile, A., Qi, B., Byeong, H. J., Bugayenko, A., Kasuno, K., Berkowitz, D. E., & Irani, K. (2005). P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction. Journal of Molecular and Cellular Cardiology, 39(6), 992-995. https://doi.org/10.1016/j.yjmcc.2005.09.003

Yamamori, T, White, AR, Mattagajasingh, I, Khanday, FA, Haile, A, Qi, B, Byeong, HJ, Bugayenko, A, Kasuno, K, Berkowitz, DE & Irani, K 2005, 'P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction', Journal of Molecular and Cellular Cardiology, vol. 39, no. 6, pp. 992-995. https://doi.org/10.1016/j.yjmcc.2005.09.003

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

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.",

keywords = "Endothelium, Nitric oxide, P66shc, Ras, Vascular tone",

author = "Tohru Yamamori and White, {Anthony R.} and Ilwola Mattagajasingh and Khanday, {Firdous A.} and Azeb Haile and Bing Qi and Byeong, {Hwa Jeon} and Artem Bugayenko and Kenji Kasuno and Berkowitz, {Dan E.} and Kaikobad Irani",

note = "Funding Information: We thank T. Finkel and S. Nemoto for the p66shc expression vector and T. Michel for the bovine eNOS cDNA. This work was supported by NIH grants R01 HL70929 and P01 HL65608 (KI), and R01 AG21523 (DEB) and by a research fellowship from the Japan Society for the Promotion of Science (JSPS) for Young Scientists (T.Y.).",

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doi = "10.1016/j.yjmcc.2005.09.003",

language = "English (US)",

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T1 - P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation

T2 - Implications for age-associated vascular dysfunction

AU - Yamamori, Tohru

AU - White, Anthony R.

AU - Mattagajasingh, Ilwola

AU - Khanday, Firdous A.

AU - Haile, Azeb

AU - Qi, Bing

AU - Byeong, Hwa Jeon

AU - Bugayenko, Artem

AU - Kasuno, Kenji

AU - Berkowitz, Dan E.

AU - Irani, Kaikobad

N1 - Funding Information: We thank T. Finkel and S. Nemoto for the p66shc expression vector and T. Michel for the bovine eNOS cDNA. This work was supported by NIH grants R01 HL70929 and P01 HL65608 (KI), and R01 AG21523 (DEB) and by a research fellowship from the Japan Society for the Promotion of Science (JSPS) for Young Scientists (T.Y.).

PY - 2005/12

Y1 - 2005/12

N2 - 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.

AB - 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.

KW - Endothelium

KW - Nitric oxide

KW - P66shc

KW - Ras

KW - Vascular tone

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

Abstract

Keywords

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