A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.
A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.
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DOI：
10.1016/j.bbrc.2014.11.118
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发表时间：
2015-01
影响因子：
3.1
通讯作者：
D. Zheng;Zehua Bian;Norihiko Furuya;Juan Alejandro Oliva Trejo;M. Takeda-Ezaki;Katsuyuki Takahashi;Yuka Hiraoka;R. Mineki;H. Taka;S. Ikeda;M. Komatsu;T. Fujimura;T. Ueno;J. Ezaki
中科院分区：
文献类型：
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作者：
D. Zheng;Zehua Bian;Norihiko Furuya;Juan Alejandro Oliva Trejo;M. Takeda-Ezaki;Katsuyuki Takahashi;Yuka Hiraoka;R. Mineki;H. Taka;S. Ikeda;M. Komatsu;T. Fujimura;T. Ueno;J. Ezaki
已经充分确定，饥饿诱导的胰岛素/IGF-I和血清氨基酸的减少有效地抑制雷帕霉素（mTor）信号传导的哺乳动物靶点以诱导自噬，自噬是骨骼肌中的主要降解细胞途径。在这项研究中，我们研究了运动对骨骼肌mTor信号的系统影响。野生型C57 BL/6 J小鼠在同步自噬诱导条件下饥饿24小时。在这些条件下，内源性LC 3-II增加，而S6激酶和S6核糖体蛋白在骨骼肌中去磷酸化，这表明mTor失活。使用GFP-LC 3转基因小鼠，还证实了骨骼肌中的荧光GFP-LC 3点增加，包括比目鱼肌、跖肌和腓肠肌，这清楚地显示了自噬体诱导。然后，这些饥饿的小鼠在跑步机上进行单次跑步（12米/分钟，2小时，倾斜10度）。令人惊讶的是，生化分析显示，运动引起的LC 3-II/LC 3-I的比例下降，以及从去磷酸化状态的S6-激酶和核糖体S6在这些骨骼肌的再磷酸化状态的反转。运动后骨骼肌GFP-LC 3斑点明显减少。这些结果表明，运动通过重新激活这些饥饿小鼠骨骼肌中的mTor信号来抑制饥饿诱导的自噬。
It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24 h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12 m/min, 2 h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice.