Regulation of Autophagy in Chick Skeletal Muscle: Effect of mTOR Inhibition
Regulation of Autophagy in Chick Skeletal Muscle: Effect of mTOR Inhibition
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DOI：
10.2141/jpsa.0190008
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发表时间：
2020-01-01
影响因子：
1.5
通讯作者：
Ishida, Aiko
中科院分区：
文献类型：
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作者：
Nakashima, Kazuki;Ishida, Aiko
骨骼肌的自噬在分解代谢条件下增加，导致肌肉萎缩。本研究探讨了雷帕霉素（mTOR）抑制鸡骨骼肌自噬的作用。我们检测了mTOR抑制剂Torin1对自噬的影响。用Torin1 （100 nM）孵育鸡肌管3小时，观察到Torin1抑制AKT （Ser473）、p70核糖体S6激酶1 （S6K1, Thr389）、S6核糖体蛋白（ser135 /236）和真核翻译起始因子4e结合蛋白1 （4E-BP1, Thr37/46）的磷酸化，这些蛋白被用来测量mTOR的活性。Torinl显著（P< 0.01）提高了自噬体形成指标LC3-II/LC3-I比值，而不影响自噬相关基因（LC3B、GABARAPL1、ATG12）的表达。此外，Torinl增加了atrogin1 /MAFbx（一种肌肉特异性泛素连接酶）mRNA的表达。禁食24小时可抑制鸡骨骼肌中AKT （Ser473）、S6K1 （Ther389）、S6核糖体蛋白（Ser235/236）和4E-BPI （Thr37/46）的磷酸化，并显著(P
Autophagy in the skeletal muscle increases under catabolic conditions resulting in muscle atrophy. This study investigated the effect of inhibition of mechanistic target of rapamycin (mTOR) on autophagy in chick skeletal muscle. We examined the effects of Torin1, an mTOR inhibitor, on autophagy. Chick myotubes were incubated with Torin1 (100 nM) for 3 h. It was observed that Torin1 inhibited the phosphorylation of AKT (Ser473), p70 ribosomal S6 kinase 1 (S6K1, Thr389), S6 ribosomal protein (Ser235/236), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1, Thr37/46), which are used for measurement of mTOR activity. Torinl significantly (P< 0.01) increased the LC3-II/LC3-I ratio, an index for autophagosome formation, while it did not influence the expression of autophagy-related genes (LC3B, GABARAPL1, and ATG12). In addition, Torinl increased atrogin-1/MAFbx (a muscle-specific ubiquitin ligase) mRNA expression. Fasting for 24 h inhibited the phosphorylation of AKT (Ser473), S6K1 (Ther389), S6 ribosomal protein (Ser235/236), and 4E-BPI (Thr37/46) in chick skeletal muscle and significantly (P