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Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity
Author(s) -
Beher Dirk,
Wu John,
Cumine Suzanne,
Kim Ki Won,
Lu ShuChen,
Atangan Larissa,
Wang Minghan
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00901.x
Subject(s) - resveratrol , peptide , sirtuin 1 , chemistry , activator (genetics) , biochemistry , enzyme , acetylation , nad+ kinase , enzyme activator , in vitro , substrate (aquarium) , biology , downregulation and upregulation , ecology , gene
Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD + ‐dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys‐SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys‐SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53‐derived peptide substrate or acetylated PGC‐1α isolated from cells, and (iii) although SIRT1 deacetylates PGC‐1α in both in vitro and cell‐based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.