Differential activation of mTOR signaling by contractile activity in skeletal muscle.
Differential activation of mTOR signaling by contractile activity in skeletal muscle.
复制标题
骨骼肌收缩活动对 mTOR 信号传导的差异激活。
DOI：
10.1152/ajpregu.00324.2003
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Fielding,RogerA
中科院分区：
文献类型：
--
作者：
Parkington,JaschaD;Siebert,AdamP;LeBrasseur,NathanK;Fielding,RogerA
收缩活动刺激骨骼肌肥大的细胞机制开始被阐明，似乎包括激活磷脂酰肌醇3-激酶信号传导底物哺乳动物雷帕霉素靶蛋白（mTOR）。我们检测了mTOR磷酸化对急性收缩活动的反应的时间过程和位置。大鼠后肢肌肉收缩活动引起的高频电刺激（HFES）的坐骨神经。跖肌（PLA），胫骨前肌（TA），比目鱼肌（Sol）从刺激和对照肢体肌肉刺激后立即或6小时收集。HFES在Pla收缩活动后立即导致mTOR磷酸化（3.4 ± 0.9倍，P< 0.01），而TA与对照组相比无变化。HFES后6 h，Pla和TA的mTOR磷酸化水平分别为3.6 ± 0.6倍和4.6 ± 0.9倍（P< 0.05）。有趣的是，mTOR激活主要发生在表达IIa型而非I型肌球蛋白重链同种型的纤维中。此外，HFES在运动后立即诱导Pla（0.4 ± 0.1倍，P< 0.05）而不是TA的适度核糖体蛋白S6激酶磷酸化，并且在Pla和TA中在运动后6 h更显著（分别为1.4 ± 0.4倍和2.4 ± 0.3倍，P< 0.01）。Akt/PKB磷酸化在两个时间点与对照相似。这些结果表明，mTOR信号在单次肌肉收缩活动后增加。尽管有报道称mTOR在Akt/PKB下游被激活，但在本研究中，HFES诱导的mTOR信号传导不依赖于Akt/PKB磷酸化。纤维类型依赖性mTOR磷酸化可能是某些纤维类型更容易发生收缩诱导肥大的分子基础。
The cellular mechanisms by which contractile activity stimulates skeletal muscle hypertrophy are beginning to be elucidated and appear to include activation of the phosphatidylinositol 3-kinase signaling substrate mammalian target of rapamycin (mTOR). We examined the time course and location of mTOR phosphorylation in response to an acute bout of contractile activity. Rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla), tibialis anterior (TA), and soleus (Sol) muscles from stimulated and control limbs were collected immediately or 6 h after stimulation. HFES resulted in mTOR phosphorylation immediately after (3.4 ± 0.9-fold,P< 0.01) contractile activity in Pla, whereas TA was unchanged compared with controls. mTOR phosphorylation remained elevated in Pla (3.6 ± 0.6-fold) and increased in TA (4.6 ± 0.9-fold,P< 0.05) 6 h after HFES. Interestingly, mTOR activation occurred predominantly in fibers expressing type IIa but not type I myosin heavy chain isoform. Furthermore, HFES induced modest ribosomal protein S6 kinase phosphorylation immediately after exercise in Pla (0.4 ± 0.1-fold,P< 0.05) but not TA and more markedly 6 h after in both Pla and TA (1.4 ± 0.4-fold vs. 2.4 ± 0.3-fold, respectively,P< 0.01). Akt/PKB phosphorylation was similar to controls at both time points. These results suggest that mTOR signaling is increased after a single bout of muscle contractile activity. Despite reports that mTOR is activated downstream of Akt/PKB, in this study, HFES induced mTOR signaling independent of Akt/PKB phosphorylation. Fiber type-dependent mTOR phosphorylation may be a molecular basis by which some fiber types are more susceptible to contraction-induced hypertrophy.