Effects of Chronic Akt/mTOR Inhibition by Rapamycin on Mechanical Overload–Induced Hypertrophy and Myosin Heavy Chain Transition in Masseter Muscle

Journal of Pharmacological Sciences

Yasutake Saeki¹  Yasumasa Mototani¹  Satoshi Okumura¹  Takayuki Fujita³  Yoshiki Nakamura²  Yoshiki Ohnuki¹  Daisuke Umeki¹  Kouichi Shiozawa¹ 

[1] Department of Physiology, Tsurumi University School of Dental Medicine, Japan;Department of Orthodontics, Tsurumi University School of Dental Medicine, Japan;Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Japan

关键词: masseter muscle;    Akt/mammalian target of rapamycin (mTOR) pathway;    hypertrophy;    myosin heavy chain;    mechanical stress;   

DOI  :  10.1254/jphs.12195FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(36)Cited-By(5)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.

【 授权许可】

Unknown