†Dirk Beher and John Wu have contributed equally.
Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity
Article first published online: 20 OCT 2009
© 2009 John Wiley & Sons A/S
Chemical Biology & Drug Design
Volume 74, Issue 6, pages 619–624, December 2009
How to Cite
Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S.-C., Atangan, L. and Wang, M. (2009), Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. Chemical Biology & Drug Design, 74: 619–624. doi: 10.1111/j.1747-0285.2009.00901.x
- Issue published online: 28 OCT 2009
- Article first published online: 20 OCT 2009
- Received 30 April 2009, revised 11 August 2009 and accepted for publication 10 September 2009
- Fluor de Lys;
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.