Redox regulation of sirtuin-1 by S-glutathiolation.
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 SIRT1 deacetylase activity, but inhibited stimulation of activity by resveratrol (RSV) with an IC(50) of 69 microM. These observations indicate that S-glutathiolation of SIRT1 by low concentrations of reactive glutathione can modulate its enzymatic activity.
Zee
Rebecca S
RS
Vascular Biology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA.
Yoo
Chris B
CB
Pimentel
David R
DR
Perlman
David H
DH
Burgoyne
Joseph R
JR
Hou
Xiuyun
X
McComb
Mark E
ME
Costello
Catherine E
CE
Cohen
Richard A
RA
Bachschmid
Markus M
MM
D002460:Cell Line; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D000077185:Resveratrol; D026422:S-Nitrosoglutathione / Q000378:metabolism*; D056564:Sirtuin 1 / Q000737:chemistry / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
D004220:Disulfides; D009603:Nitroso Compounds; D011506:Proteins; D013267:Stilbenes; D026422:S-Nitrosoglutathione; D056564:Sirtuin 1; D005978:Glutathione; D003545:Cysteine; D000077185:Resveratrol
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