Abstract

Sirtuin-1 (SIRT1) is an NAD+-dependent protein deacetylase that is sensitive to oxidative signals. Our purpose was to determine whether SIRT1 activity is sensitive to the low molecular weight nitrosothiol, S-nitrosoglutathione (GSNO), which can transduce oxidative signals into physiological responses. SIRT1 formed mixed disulfides with GSNO-Sepharose, and mass spectrometry identified several cysteines that are modified by GSNO, including Cys-67 which was S-glutathiolated. GSNO had no effect on basal SIRT1deacetylase activity, but inhibited stimulation of activity by resveratrol (RSV) with an IC50 of 69 μM. These observations indicate that S-glutathiolation of SIRT1 by low concentrations of reactive glutathione can modulate its enzymatic activity.
Antioxid. Redox Signal. 13, 1023–1032.

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Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 13Issue Number 7October 1, 2010
Pages: 1023 - 1032
PubMed: 20392170

History

Published in print: October 1, 2010
Published online: 19 August 2010
Published ahead of print: 30 June 2010
Published ahead of production: 14 April 2010
Accepted: 14 April 2010
Received: 13 April 2010

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Rebecca S. Zee
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Chris B. Yoo
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
David R. Pimentel
Myocardial Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
David H. Perlman
Cardiovascular Proteomics Center, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Joseph R. Burgoyne
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Xiuyun Hou
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Mark E. McComb
Cardiovascular Proteomics Center, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Catherine E. Costello
Cardiovascular Proteomics Center, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Richard A. Cohen
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
Markus M. Bachschmid
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.

Notes

Address correspondence to:Markus Michael BachschmidBoston University Medical CenterVascular Biology Unit X720650 Albany StreetBoston, MA 02118E-mail: [email protected]

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