Cessation of electrically-induced muscle contraction activates autophagy in cultured myotubes.
Cessation of electrically-induced muscle contraction activates autophagy in cultured myotubes.
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DOI：
10.1016/j.bbrc.2020.09.009
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发表时间：
2020-09
影响因子：
3.1
通讯作者：
K. Yoshioka;Nobuaki Sasai;Yuko Kurogi;K. Hayakawa;Yuta Itoh;Nobuhide Agata;T. Murakami;Masumi Inoue-Miyazu;M. Sokabe;K. Kawakami
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文献类型：
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作者：
K. Yoshioka;Nobuaki Sasai;Yuko Kurogi;K. Hayakawa;Yuta Itoh;Nobuhide Agata;T. Murakami;Masumi Inoue-Miyazu;M. Sokabe;K. Kawakami
众所周知，锻炼可以改善骨骼肌功能。其机制涉及肌肉收缩诱导的mTOR通路的激活，该通路在蛋白质合成中发挥核心作用。然而，mTOR的激活阻止了自噬，自噬是一种在细胞维持/内稳态中起关键作用的循环机制。这两种对肌肉收缩的反应看起来与运动的功能改善相矛盾。在这里，我们在一种培养的肌管模型中研究了在一系列活动-非活动阶段的这些矛盾的肌肉反应，该模型接受电刺激以诱导间歇性肌肉收缩。我们的模型表明：(1)收缩活动诱导mTOR激活和肌肉肥大，但阻止自噬，导致受损蛋白质的积累；(2)肌肉停止收缩迅速激活自噬，去除受损蛋白质，但长时间的静止状态会导致肌肉萎缩。我们的发现为肌肉生物学提供了新的见解，并表明不仅肌肉收缩，而且随后的收缩停止对骨骼肌功能的改善起着实质性的作用。
Exercise is known to improve skeletal muscle function. The mechanism involves muscle contraction-induced activation of the mTOR pathway, which plays a central role in protein synthesis. However, mTOR activation blocks autophagy, a recycling mechanism with a critical role in cellular maintenance/homeostasis. These two responses to muscle contraction look contradictory to the functional improvement of exercise. Herein, we investigate these paradoxical muscle responses in a series of active–inactive phases in a cultured myotube model receiving electrical stimulation to induce intermittent muscle contraction. Our model shows that (1) contractile activity induces mTOR activation and muscle hypertrophy but blocks autophagy, resulting in the accumulation of damaged proteins, while (2) cessation of muscle contraction rapidly activates autophagy, removing damaged protein, yet a prolonged inactive state results in muscle atrophy. Our findings provide new insights into muscle biology and suggest that not only muscle contraction, but also the subsequent cessation of contraction plays a substantial role for the improvement of skeletal muscle function.