Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy.
Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy.
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DOI：
10.1016/j.yjmcc.2011.01.008
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发表时间：
2011-10
影响因子：
5
通讯作者：
Gupta MP
中科院分区：
文献类型：
--
作者：
Sundaresan NR;Pillai VB;Gupta MP
限制卡路里摄入被认为是为哺乳动物提供健康益处的最佳环境干预措施。这种干预的潜在机制似乎由一组依赖NAD的脱乙酰酶控制，统称为sirtuins。在哺乳动物中，有七个sirutuin类似物，SIRT1到SIRT7。作为该家族的创始成员，SIRT1被证明以一种剂量依赖的方式保护心肌细胞免受凋亡和年龄依赖性退化的影响--在低剂量时保护细胞，但在高剂量时显示出有害的影响。SIRT1过表达或下调的研究表明，尽管它保护细胞免受氧化应激和缺血再灌注损伤，但它促进了心肌细胞的肥大。白藜芦醇对内源性SIRT1的激活也显示出SIRT1的促生存和促肥大活性。本文综述了SIRT1在调节应激状态下心肌细胞生长和存活中的作用，以及其心脏保护作用的机制。我们还简要讨论了另外两个已被证明具有心脏保护作用的sirtuin类似物。
Calorie restriction is considered to be the best environmental intervention providing health benefits to mammals. The underlying mechanism of this intervention seems to be controlled by a group of NAD-dependent deacetylases, collectively called sirtuins. In mammals there are seven sirutuin analogues, SIRT1 to SIRT7. The founding member of this family, SIRT1 is shown to protect cardiomyocytes from apoptosis and age-dependent degeneration in a dose dependent manner—protecting cells at low doses but showing detrimental effects at high doses. Studies performed with over expression or knockdown of SIRT1 indicated that though it protects cells from oxidative stress and ischemia-reperfusion injury, it promotes hypertrophy of cardiomyocytes. Activation of endogenous SIRT1 by resveratrol also displayed pro-survival and pro-hypertrophic activity of SIRT1. In this article we review recent findings documenting the role of SIRT1 in regulating cardiac myocyte growth and survival under stress, and the proposed mechanism behind its cardio protective effects. We also briefly discuss two other sirtuin analogues which have been shown to have cardioprotective effects.