title: Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.
abstract: 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.
authors.affiliation: Department of Physiology, Tsurumi University School of Dental Medicine, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Umeki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ohnuki
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Mototani
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shiozawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Saeki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okumura
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001732:Bite Force; D019703:Calcineurin / Q000502:physiology; D006984:Hypertrophy / Q000209:etiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008406:Masseter Muscle / Q000002:abnormalities* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020033:Protein Isoforms; C546845:mTOR protein, rat; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D018995:Myosin Heavy Chains; D020123:Sirolimus