Ogasawara Riki, Fujita Satoshi, Hornberger Troy A, Kitaoka Yu, Makanae Yuhei, Nakazato Koichi, Naokata Ishii
Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Nagoya, Japan.
Department of Life Sciences, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2016 Aug 9;6:31142. doi: 10.1038/srep31142.
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.
抗阻运动(RE)可激活雷帕霉素哺乳动物靶蛋白(mTOR)信号通路,有人提出,对雷帕霉素敏感的mTOR信号通路控制着RE诱导的蛋白质合成、核糖体生物合成、自噬以及过氧化物酶体增殖物激活受体γ共激活因子1α(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,我们研究了对雷帕霉素敏感的mTOR在RE诱导的肌肉蛋白质合成激活、核糖体生物合成、PGC-1α表达和肥大中的作用。结果表明,抑制对雷帕霉素敏感的mTOR可阻止RE诱导的核糖体生物合成,但仅部分抑制肌肉蛋白质合成的激活。同样,抑制对雷帕霉素敏感的mTOR仅部分阻断慢性RE的肥大效应。此外,急性和慢性RE均促进了PGC-1α表达的增加,这些改变不受抑制对雷帕霉素敏感的mTOR的影响。综合来看,本研究结果不仅证实对雷帕霉素敏感的mTOR在RE诱导的蛋白质合成激活和肥大诱导中起重要作用,还表明其他(独立于对雷帕霉素敏感的mTOR的)机制也促成了这些至关重要的事件。