Literature Search and Review
Abstract
L I T E R AT U R E S E A R C H A N D R E V I E W Literature Search and Review Doug Auld, Anton Simeonov, and Craig Thomas National Institutes of Health, Bethesda, Maryland. RETHINKING RESVERATROL Beher D, Wu J, Cumine S, Kim KW, Lu S-C, Atangan L, et al. Resveratrol is not a direct activator of SIRT1. Chem Biol Drug Des 2009;74:619â624. Abstract: Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects that 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 an acetylated PGC-1α isolated from cells, and (iii) although SIRT1