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The Role of Rapamycin‐Insensitive mTOR Signaling in the Regulation of Muscle Protein Synthesis in a Rat Model of Resistance Exercise
Author(s) -
Ogasawara Riki,
Suginohara Takeshi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1036.12
Subject(s) - pi3k/akt/mtor pathway , mtorc1 , phosphorylation , mtorc2 , protein kinase b , pharmacology , chemistry , biology , medicine , signal transduction , microbiology and biotechnology
Resistance exercise (RE) activates signaling by the mammalian target of rapamycin (mTOR), and it has been suggested that rapamycin‐sensitive mTOR signaling is necessary for the increase in muscle protein synthesis (MPS) after RE. However, recent studies have reported that rapamycin does not completely inhibit the RE‐induced increase in MPS, suggesting that rapamycin‐sensitive mTOR‐independent (rapamycin‐insensitive mTOR and mTOR‐independent) mechanisms contribute to this event. The aim of this study was to investigate whether rapamycin‐insensitive mTOR signaling plays a role in the regulation of RE‐induced increase in MPS. The right gastrocnemius muscle of male Sprague‐Dawley rats aged 11 weeks was isometrically contracted via percutaneous electrical stimulation (100Hz, 5 sets of ten 3‐s contractions, 7‐s rest between contractions, 3 min rest between sets), while the left gastrocnemius muscle served as a control. Placebo, allosteric mTOR inhibitor rapamycin, or ATP‐competitive mTOR inhibitor AZD8055 was injected intraperitoneally 1 h before RE. Muscle samples were obtained 1 and 6 h after a bout of RE. RE increased MPS (measured by) at both time points after RE in placebo group. Rapamycin completely inhibited RE‐induced MPS 1 h, but not 6 h, after RE. On the other hand, AZD8055 completely inhibited RE‐induced MPS at both time points after RE. The phosphorylation of p70S6K at Thr389 and 4E‐BP1 at Thr37/46, which are downstream targets of mTORC1, was sensitive to both rapamycin and AZD8055. However, inhibition of 4E‐BP1 phosphorylation was more pronounced by AZD8055. Moreover, only AZD8055 inhibited the phosphorylation of Akt at Ser473, a downstream target of mTORC2. We conclude that RE‐induced increase in MPS is mTOR signaling‐dependent process, and furthermore, both rapamycin‐sensitive and ‐insensitive mTOR signaling regulate this event. Support or Funding Information This work was supported by JSPS KAKENHI Grant No. 267028.