Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle

To examine the effects of the akt/mammalian target of rapamycin (mtor) pathway on masseter muscle hypertrophy and myosin heavy chain (mhc) transition in response to mechanical overload,we analyzed the effects of bite-opening (bo) on the hypertrophy and mhc composition of masseter muscle of bo-rats treated or not treated with rapamycin (rapa),a selective mtor inhibitor. the masseter muscle weight in bo-rats was significantly greater than that in controls,and this increase was attenuated by rapa treatment. expression of slow-twitch mhc isoforms was significantly increased in bo-rats with/without rapa treatment,compared with controls,but the magnitude of the increase was much smaller in rapa-treated bo-rats. phosphorylation of p44/42 mapk (erk1/2),which preserves fast-twitch mhc isoforms in skeletal muscle,was significantly decreased in bo-rats,but the decrease was abrogated by rapa treatment. calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow mhc isoform transition,but expression of known calcineurin activity modulators was unaffected by rapa treatment. taken together,these results indicate that the akt/mtor pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow mhc isoform transition in response to mechanical overload with inhibition of the erk1/2 pathway and operates independently of the calcineurin pathway. © the japanese pharmacological society.