The role of mTOR signalling in the regulation of skeletal muscle mass in a rodent model of resistance exercise.
The role of mTOR signalling in the regulation of skeletal muscle mass in a rodent model of resistance exercise.
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DOI：
10.1038/srep31142
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发表时间：
2016-08-09
影响因子：
4.6
通讯作者：
Naokata I
中科院分区：
文献类型：
--
作者：
Ogasawara R;Fujita S;Hornberger TA;Kitaoka Y;Makanae Y;Nakazato K;Naokata I
抗阻运动（RE）通过哺乳动物雷帕霉素靶蛋白（mTOR）激活信号传导，并且已经表明雷帕霉素敏感的mTOR信号传导控制RE诱导的蛋白质合成、核糖体生物合成、自噬和过氧化物酶体增殖物γ共激活因子1 α（PGC-1α）表达的变化。然而，缺乏支持上述关系的直接证据。因此，在本研究中，我们研究了雷帕霉素敏感的mTOR在RE诱导的肌肉蛋白质合成、核糖体生物合成、PGC-1α表达和肥大激活中的作用。结果表明，抑制雷帕霉素敏感的mTOR可以阻止RE诱导的核糖体生物合成，但它只能部分抑制肌肉蛋白质合成的激活。同样，抑制雷帕霉素敏感的mTOR仅部分阻断慢性RE的肥大作用。此外，急性和慢性RE均促进PGC-1α表达的增加，这些变化不受雷帕霉素敏感性mTOR抑制的影响。结合起来，这项研究的结果不仅确定了雷帕霉素敏感的mTOR在RE诱导的蛋白质合成激活和诱导肥大中起着重要作用，而且还证明了其他（雷帕霉素敏感的mTOR非依赖性）机制有助于这些根本性的重要事件。
Resistance exercise (RE) activates signalling by the mammalian target of rapamycin (mTOR), and it has been suggested that rapamycin-sensitive mTOR signalling controls RE-induced changes in protein synthesis, ribosome biogenesis, autophagy, and the expression of peroxisome proliferator gamma coactivator 1 alpha (PGC-1α). However, direct evidence to support the aforementioned relationships is lacking. Therefore, in this study, we investigated the role of rapamycin-sensitive mTOR in the RE-induced activation of muscle protein synthesis, ribosome biogenesis, PGC-1α expression and hypertrophy. The results indicated that the inhibition of rapamycin-sensitive mTOR could prevent the induction of ribosome biogenesis by RE, but it only partially inhibited the activation of muscle protein synthesis. Likewise, the inhibition of rapamycin-sensitive mTOR only partially blocked the hypertrophic effects of chronic RE. Furthermore, both acute and chronic RE promoted an increase in PGC-1α expression and these alterations were not affected by the inhibition of rapamycin-sensitive mTOR. Combined, the results from this study not only establish that rapamycin-sensitive mTOR plays an important role in the RE-induced activation of protein synthesis and the induction of hypertrophy, but they also demonstrate that additional (rapamycin-sensitive mTOR-independent) mechanisms contribute to these fundamentally important events.