SIRT1IsRequiredforAMPKActivation翻译.doc

SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function AMPK激活和SIRT1是分不开的，res对线粒体功能的有效作用 SUMMARY Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent （避免）the developmental defects of germline SIRT1 knockouts, we have developed an inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation, and increased NAD+ levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits. A mouse overexpressing SIRT1 mimicked these effects. A high dose of resveratrol activated AMPK in a SIRT1-independent manner, demonstrating that resveratrol dosage is a critical factor. Importantly, at both doses of resveratrol no improvements in mitochondrial function were observed in animals lacking SIRT1. Res诱导线粒体功能，防止代谢下降，但是sirt1是否能够介导这些作用是值得讨论的主题，为了避免敲出了sirt1种系的发育缺陷，我们研究了诱导系统，它能够允许成年老鼠全身sirt1删除。用适当浓度res处理过的老鼠展示了线粒体生物合成和功能，AMPK激活的增强，还有骨骼肌的中NAD+水平增强，然而敲出SIRT1不能表现出这些优点。老鼠过度表达SIRT1模拟这些作用。高剂量的res是以不依赖sirt1的方式激活了AMPK（低浓度的res是依赖sirt1的方式激活AMPK），展示了res的剂量是重要因素。最重要是这两个剂量的res在缺乏sirt1的动物中线粒体功能没有提高。 Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo.这些数据说明了在res合适的浓度下sirt1在体内体外激活AMPK和提高线粒体功能起到非常大作用。 INTRODUCTION The mammalian sirtuins (SIRT1–SIRT7) are a conserved family of NAD+-dependent deacetylases and ADP-ribosyltransferases involved in numerous fundamental cellular processes including gene silencing, DNA repair, and metabolic regulation (Baur et al., 2010; Donmez and Guarente, 2010; Haigis and Sinclair,2010). Deletion of SIRT1 in outbred strains of mice abrogates the effect of caloric restriction (CR) on physical activity (Chen et al., 2005) an