Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse
Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse
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DOI：
10.1152/japplphysiol.91451.2008
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发表时间：
2009-12-01
影响因子：
3.3
通讯作者：
Hood, David A.
中科院分区：
文献类型：
--
作者：
Chabi, Beatrice;Adhihetty, Peter J.;Hood, David A.
Chabi B，Adhihetty PJ，O‘Leary MF，Menzies KJ，Hood DA。慢性肌肉使用和废弃状态下Sirt1表达与线粒体蛋白的关系应用生理学杂志107：1730-1735,2009。Sirt1是一种依赖NAD(+)的组蛋白去乙酰化酶，与线粒体生物发生PGC-1α的调节蛋白相互作用，对代谢变化敏感。我们评估了Sirt1、线粒体蛋白和PGC-1α的表达之间是否存在严格的关系，在具有广泛氧化能力的组织中，以及在长期使用(自愿车轮运行或电刺激7天，10赫兹；3小时/天)或停用(失神经长达21天)的骨骼肌中，细胞器的生物发生发生了变化。PGC-1α水平与Sirt1的表达并不密切相关，通过免疫印迹或通过酶促脱乙酰酶活性来测量。跑步动物比目鱼肌和足底肌线粒体膜蛋白细胞色素c增加70-90%，而Sirt1活性不变。在慢性刺激的肌肉中，细胞色素c比未刺激的肌肉增加30%，而Sirt1的活性略有增加20%-25%。相反，在失神经肌肉中，线粒体含量的这些标志物与对照肌肉相比降低了30%-50%，而Sirt1活性增加了75%-80%。我们的数据表明，Sirt1和PGC-1α的表达是独立调控的，尽管Sirt1活性可能参与线粒体的生物发生，但其表达与慢性肌肉使用和停用条件下线粒体蛋白质的变化并不密切相关。
Chabi B, Adhihetty PJ, O'Leary MF, Menzies KJ, Hood DA. Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse. J Appl Physiol 107: 1730-1735, 2009. First published October 1, 2009; doi:10.1152/japplphysiol.91451.2008.-Sirt1 is a NAD(+)-dependent histone deacetylase that interacts with the regulatory protein of mitochondrial biogenesis PGC-1 alpha and is sensitive to metabolic alterations. We assessed whether a strict relationship between the expression of Sirt1, mitochondrial proteins, and PGC-1 alpha existed across tissues possessing a wide range of oxidative capabilities, as well as in skeletal muscle subject to chronic use (voluntary wheel running or electrical stimulation for 7 days, 10 Hz; 3 h/day) or disuse (denervation for up to 21 days) in which organelle biogenesis is altered. PGC-1 alpha levels were not closely associated with the expression of Sirt1, measured using immunoblotting or via enzymatic deacetylase activity. The mitochondrial protein cytochrome c increased by 70-90% in soleus and plantaris muscles of running animals, whereas Sirt1 activity remained unchanged. In chronically stimulated muscle, cytochrome c was increased by 30% compared with nonstimulated muscle, whereas Sirt1 activity was increased modestly by 20-25%. In contrast, in denervated muscle, these markers of mitochondrial content were decreased by 30-50% compared with the control muscle, whereas Sirt1 activity was increased by 75-80%. Our data suggest that Sirt1 and PGC-1 alpha expression are independently regulated and that, although Sirt1 activity may be involved in mitochondrial biogenesis, its expression is not closely correlated to changes in mitochondrial proteins during conditions of chronic muscle use and disuse.