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

J Pharmacol Sci. 2013;122(4):278-88. doi: 10.1254/jphs.12195fp. Epub 2013 Jul 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bite Force
  • Calcineurin / physiology
  • Hypertrophy / etiology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Masseter Muscle / abnormalities*
  • Masseter Muscle / metabolism*
  • Myosin Heavy Chains / metabolism*
  • Oncogene Protein v-akt / antagonists & inhibitors*
  • Organ Size / drug effects
  • Phosphorylation
  • Protein Isoforms
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Sirolimus / pharmacology*
  • Stress, Mechanical*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Protein Isoforms
  • mTOR protein, rat
  • Oncogene Protein v-akt
  • TOR Serine-Threonine Kinases
  • Calcineurin
  • Myosin Heavy Chains
  • Sirolimus

Supplementary concepts

  • Masticatory Muscles, Hypertrophy of