期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 285, 期 5, 页码 R1086-R1090出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00324.2003
关键词
exercise; hypertrophy; ribosomal protein S6 kinase; Akt
类别
资金
- NATIONAL INSTITUTE ON AGING [R01AG018844] Funding Source: NIH RePORTER
- NIA NIH HHS [AG-18844] Funding Source: Medline
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.
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