Sirtuin 1-mediated Effects of Exercise and Resveratrol on Mitochondrial Biogenesis

Sirtuin 1-mediated Effects of Exercise and Resveratrol on Mitochondrial Biogenesis
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DOI:
10.1074/jbc.m112.431155
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发表时间:
2013-03-08
影响因子:
4.8
通讯作者:
Hood, David A.
Hood, David A.
中科院分区:
生物学2区
文献类型:
--
作者:
Menzies, Keir J.;Singh, Kaustabh;Hood, David A.

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本研究的目的是评价sirtuin 1(SirT1)在运动和白藜芦醇(RSV)诱导的骨骼肌线粒体生物发生中的作用。利用肌肉特异性SirT1缺陷(KO)小鼠和分化肌管细胞培养模型,比较了SirT1激活剂白藜芦醇和运动诱导线粒体生物发生的作用。这些实验表明,SirT1在维持线粒体基本含量方面作用不大,而在维持线粒体功能方面发挥了较大作用。此外,自愿运动和RSV治疗以不依赖于SirT1的方式诱导线粒体生物发生。然而,当RSV和运动相结合时,SirT1依赖的协同效应明显,导致PGC-1α和SirT1的核转位增加,并刺激线粒体的生物发生。因此,RSV对肌肉线粒体生物发生的影响程度取决于SirT1以及细胞环境,例如反复运动产生的环境。
The purpose of this study was to evaluate the role of sirtuin 1 (SirT1) in exercise-and resveratrol (RSV)-induced skeletal muscle mitochondrial biogenesis. Using muscle-specific SirT1-deficient (KO) mice and a cell culture model of differentiated myotubes, we compared the treatment of resveratrol, an activator of SirT1, with that of exercise in inducing mitochondrial biogenesis. These experiments demonstrated that SirT1 plays a modest role in maintaining basal mitochondrial content and a larger role in preserving mitochondrial function. Furthermore, voluntary exercise and RSV treatment induced mitochondrial biogenesis in a SirT1-independent manner. However, when RSV and exercise were combined, a SirT1-dependent synergistic effect was evident, leading to enhanced translocation ofPGC-1 alpha and SirT1 to the nucleus and stimulation of mitochondrial biogenesis. Thus, the magnitude of the effect of RSV on muscle mitochondrial biogenesis is reliant on SirT1, as well as the cellular environment, such as that produced by repeated bouts of exercise.