PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle
PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle
复制标题
PGC-1α 促进运动诱导的小鼠骨骼肌自噬
DOI：
10.14814/phy2.12698
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发表时间：
2016-02-01
影响因子：
2.5
通讯作者：
Pilegaard, Henriette
中科院分区：
文献类型：
--
作者：
Halling, Jens F.;Ringholm, Stine;Pilegaard, Henriette
最近的证据表明，运动通过激活自噬来刺激骨骼肌细胞成分的降解，但运动恢复期间自噬反应的时间过程尚未确定。此外，运动诱导的自噬背后的调节机制仍不清楚，尽管肌肉氧化表型与基础自噬水平有关。因此，本研究的目的是研究肌肉氧化能力的关键调节因子PGC-1 α在恢复过程中的几个时间点在运动诱导的自噬中的作用。将具有PGC-1 α的转基因肌肉特异性过表达（TG）或敲除（MKO）的小鼠及其各自的同窝对照进行单次1小时的跑步机跑步，并在运动后立即（0小时）、2、6和10小时实施安乐死。在PGC-1 α MKO品系中，自噬标志物LC 3 II的四头肌蛋白含量在lox/lox对照中从2小时到恢复期增加，但在MKO小鼠中没有。在PGC-1 α TG菌株中，从运动后2小时开始，TG中LC 3 II的四头肌蛋白含量增加，但WT中没有。尽管AMPK和ACC磷酸化在运动后立即增加，但观察到的运动诱导的自噬反应与AMPK靶点ULK 1的磷酸化无关。然而，较低的蛋白质羰基含量观察到在lox/lox和TG小鼠运动后与增加的LC 3脂化。总之，本研究结果表明，骨骼肌PGC-1 α在协调几个运动诱导的适应性反应，包括自噬去除受损的细胞成分的作用。
Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise-induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC-1 alpha, in exercise-induced autophagy at several time points during recovery. Mice with transgenic muscle-specific overexpression (TG) or knockout (MKO) of PGC-1 alpha and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC-1 alpha MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC-1 alpha TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise-induced autophagy response was not associated with phosphorylation of the AMPK-target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC-1 alpha in coordinating several exercise-induced adaptive responses including autophagic removal of damaged cellular components.