期刊
CHEMBIOCHEM
卷 17, 期 1, 页码 77-81出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201500482
关键词
enzymes; ethanolamides; natural products; quercetin; sirtuins
资金
- National Institute on Aging (NIA) Intramural Research Program
- Academy of Finland [137788, 269341]
- Orion-Farmos Research Foundation
- Saastamoinen Foundation
- NATIONAL INSTITUTE ON AGING [ZIAAG000295] Funding Source: NIH RePORTER
Sirtuin6 (SIRT6) is an NAD+-dependent histone deacetylase enzyme that is involved in multiple molecular pathways related to aging. Initially, it was reported that SIRT6 selectively deacetylated H3K9Ac and H3K56Ac; however, it has more recently been shown to preferentially hydrolyze long-chain fatty acyl groups over acetyl groups in vitro. Subsequently, fatty acids were demonstrated to increase the catalytic activity of SIRT6. In this study, we investigated whether a series of N-acylethanolamines (NAEs), quercetin, and luteolin could regulate SIRT6 activity. NAEs increased SIRT6 activity, with oleoylethanolamide having the strongest activity (EC50 value of 3.1m). Quercetin and luteolin were demonstrated to have dual functionality with respect to SIRT6 activity; namely, they inhibited SIRT6 activity with IC50 values of 24 and 2m, respectively, and stimulated SIRT6 activity more than sixfold (EC50 values of 990 and 270m, respectively).
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