Hydrogen Peroxide Does Not Potentiate Exercise-induced Mtorc1 In Rat Skeletal Muscle

Abstract

Our previous study showed that administration of an antioxidant attenuated the phosphorylation of p70S6K and skeletal muscle hypertrophy induced by mechanical overload (Makanae et al. 2013), suggesting that reactive oxygen species (ROS) could be an activator of mammalian target of rapamycin complex 1(mTORC1), a key regulator of muscle protein synthesis. However, no study has investigated the effects of exogenous injection of ROS into skeletal muscle on the mTORC1 activity. PURPOSE: The purpose of this sturdy was to investigate the effect of ROS injection on mTORC1 activity at baseline and after a bout of exercise in rat skeletal muscle. METHODS: Experiment 1: The male Sprague-Dawley rats, at 11 weeks of age, were injected with hydrogen peroxide (1 mM, 0.1 mL) or placebo (PBS, 0.1 mL) into the right gastrocnemius muscle under isoflurane anesthesia, and killed by blood removal at 1 h after the injection. Experiment 2: The right gastrocnemius muscle of the rats was isometrically exercised (stimulating 3 sec × 10 contractions, with a 7 sec interval between contractions, per set for 5 sets, with 3 min rest intervals) via percutaneous electrical stimulation under isoflurane anesthesia. The hydrogen peroxide or placebo were injected into the right gastrocnemius muscle immediately after the resistance exercise. RESULTS: The injection of hydrogen peroxide increased significantly the phosphorylation of p70S6K (Thr389) and rspS6 (Ser235/Ser236) at 1 h after the injection (P < 0.05) as compared to the placebo injection. Resistance exercise increased the phosphorylation of p70S6K (Thr389) and prS6 (Ser235/Ser236) at 3 h after exercise in the both hydrogen peroxide and placebo injected groups. However, there was no difference in the level of either p70S6K (Thr389) or prS6 (Ser235/Ser236) phosphorylation between groups. CONCLUSIONS: These results suggest that ROS is one of the activator of mTORC1 signaling in the skeletal muscle, but the exogenous increase in ROS does not further stimulate resistance exercise-induced mTORC1 activation.