Effects of Chronic Akt/mTOR Inhibition by Rapamycin on Mechanical Overload–Induced Hypertrophy and Myosin Heavy Chain Transition in Masseter Muscle
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概要
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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.
著者
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Saeki Yasutake
Department Of Physialogy Tsurumi Univ. School Of Dental Medicine
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Ohnuki Yoshiki
Department Of Physiology Tsurumi University School Of Dental Medicine
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Umeki Daisuke
Department Of Orthodontics Tsurumi University School Of Dental Medicine
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Shiozawa Kouichi
Department Of Physiology Tsurumi University School Of Dental Medicine
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Fujita Takayuki
Cardiovascular Research Institute Yokohama City University Graduate School Of Medicine
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Okumura Satoshi
Department Of Cardilogy Nippon Medical School
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Nakamura Yoshiki
Department Of Built Environment Interdisciplinary Graduate School Of Science And Engineering Tokyo I
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Mototani Yasumasa
Department of Physiology, Tsurumi University School of Dental Medicine, Japan
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MOTOTANI Yasumasa
Department of Physiology, Tsurumi University School of Dental Medicine
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Okumura Satoshi
Department of Physiology, Tsurumi University School of Dental Medicine, Japan
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Fujita Takayuki
Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Japan
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Umeki Daisuke
Department of Physiology, Tsurumi University School of Dental Medicine, Japan
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Ohnuki Yoshiki
Department of Physiology, Tsurumi University School of Dental Medicine, Japan
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Saeki Yasutake
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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