Rapamycin-insensitive mechanistic target of rapamycin regulates basal and resistance exercise-induced muscle protein synthesis

Article

关键词: HUMAN SKELETAL-MUSCLE;    INSULIN-RESISTANCE;    IN-VIVO;    MTOR;    PHOSPHORYLATION;    HYPERTROPHY;    METABOLISM;    GROWTH;    PRAS40;    AMPK;   

DOI  :  10.1096/fj.201701422R

来源: SCIE

【 摘 要 】

We investigated whether rapamycin-insensitive mechanistic target of rapamycin (mTOR) signaling plays a role in regulating resistance exercise-induced muscle protein synthesis. We used a rodent model of resistance exercise and compared the effect of rapamycin, an allosteric mTOR inhibitor, with the effect of AZD8055, an ATP-competitive mTOR kinase inhibitor. The right gastrocnemius muscle of male Sprague-Dawley rats age 11 wk was contracted isometrically via percutaneous electrical stimulation (100 Hz, 5 sets of ten 3-s contractions, 7 s of rest between contractions, 3 min of rest between sets), and the left gastrocnemius muscle served as control. Vehicle, rapamycin, or AZD8055 were intraperitoneally injected 1 h before resistance exercise. Results indicated that both rapamycin and AZD8055 inhibited mTOR complex 1 (mTORC1)/70-kDa ribosomal protein S6 kinase signaling similarly, whereas mTORC1/eukaryotic translation initiation factor 4E-binding protein 1 signaling was greatly inhibited by AZD8055. Moreover, only AZD8055 inhibited the phosphorylation of Akt at Ser473, a downstream target of mTORC2. AZD8055, but not rapamycin, completely inhibited the resistance exercise-induced increase in muscle protein synthesis. We conclude that the resistance exercise-induced increase in muscle protein synthesis is an mTOR signaling-dependent process. Furthermore, both rapamycin-sensitive and -insensitive mTOR signaling regulate this event.Ogasawara, R., Suginohara, T. Rapamycin-insensitive mechanistic target of rapamycin regulates basal and resistance exercise-induced muscle protein synthesis.

【 授权许可】

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