Substrate-specific activation of sirtuins by resveratrol
Substrate-specific activation of sirtuins by resveratrol
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DOI：
10.1074/jbc.m500655200
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发表时间：
2005-04-29
影响因子：
4.8
通讯作者：
Kennedy, BK
中科院分区：
文献类型：
--
作者：
Kaeberlein, M;McDonagh, T;Kennedy, BK
白藜芦醇是红酒中发现的一种小分子，据报道可以延缓简单真核生物的衰老，并被认为是一种潜在的卡路里限制模拟物。据报道，白藜芦醇也可作为去乙酰化酶激活剂，并且这一特性被认为是其抗衰老作用的原因。我们在此表明，白藜芦醇是酵母 Sir2 和人 SirT1 的底物特异性激活剂。特别是，我们在体外观察到，白藜芦醇增强含有 Fluor de Lys（一种非生理荧光部分）的肽底物的结合和脱乙酰化，但对缺乏荧光团的乙酰化肽的结合和脱乙酰化没有影响。与这些生化数据一致，我们发现在三种不同的酵母菌株背景中，通过 rDNA 重组、端粒附近的转录沉默和寿命来测量，白藜芦醇对体内 Sir2 活性没有可检测到的影响。根据这些发现，应该重新审视白藜芦醇假定的长寿效应的机制。
Resveratrol, a small molecule found in red wine, is reported to slow aging in simple eukaryotes and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to act as a sirtuin activator, and this property has been proposed to account for its anti-aging effects. We show here that resveratrol is a substrate-specific activator of yeast Sir2 and human SirT1. In particular, we observed that, in vitro, resveratrol enhances binding and deacetylation of peptide substrates that contain Fluor de Lys, a non-physiological fluorescent moiety, but has no effect on binding and deacetylation of acetylated peptides lacking the fluorophore. Consistent with these biochemical data we found that in three different yeast strain backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and life span. In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined.