Journal
FASEB JOURNAL
Volume 32, Issue 11, Pages 5824-5834Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201701422R
Keywords
skeletal muscle; contraction; translation; metabolism; AZD8055
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Funding
- Japan Society for the Promotion of Science [26702028]
- Grants-in-Aid for Scientific Research [26702028] Funding Source: KAKEN
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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.
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