Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB144

Poster Communications

Skeletal muscle unfolded protein response is different during muscle growth achieved by resistance training or its "mimetic" myostatin/activin blocker.

J. Hentilä1, J. Ahtiainen1, O. Ritvos2, A. Mero1, J. Hulmi1,2

1. Neuromuscular Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyvaskylä, Finland. 2. Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Accumulation of misfolded proteins into the endoplasmic reticulum (ER) is termed ER stress. It activates unfolded protein response (UPR) (1) which has a role in muscle function regulation (2). Resistance exercise (RE) probably remains the best option to increase muscle hypertrophy and strength, but "exercise mimetics" may provide a pharmacological option to prevent muscle loss in the future. RE (3,4) and its "pharmacological mimetics" myostatin/activin blockers (5) both increase muscle protein synthesis and hypertrophy. However, the effect of these two different stimulus to induce muscle growth on UPR is not well known. The aim of this study was to elucidate from the previously collected muscle samples the effects of resistance exercise and training in untrained young men as well as administration of soluble activin receptor 2B (sACVR) to block myostatin and activins in healthy mice on UPR. Untrained healthy men (27±4 years, n=12) performed a resistance exercise bout in leg press (5 x 10 RM) and muscle biopsies were obtained 1 and 48 hours after the RE bout as well as after 21 weeks of resistance training (RT) from vastus lateralis (VL) muscle. Male, 6-7-week-old C57Bl/10SnJ mice were administered with sACVR (produced in house; i.p. 10 mg/kg,) or placebo (PBS; n=6) and were euthanized by cervical dislocation under isoflurane anaesthesia 1 or 2 days after a single sACVR administration (n=6 in each group) or after 2 weeks of sACVR (n=12) or PBS (n=6) administration. UPR markers were analysed by western blot and RT-qPCR. Holm-Bonferroni corrected t-tests were used to analyse RE and RT effects. One-way Anova followed by Holm-Bonferroni corrected LSD test was used to analyse 1 and 2 d sACVR effects. Student's t-test was used to analyse 2 week effects of sACVR administration. Statistical significance was set at p<0.05. Both resistance exercise/training and sACVR administration led to rather similarly increased mTOR-signaling and muscle hypertrophy (4,5). Now we showed that several UPR indicators (PERK, ATF4, GRP78 and Xbp1s) were increased (p<0.05) at 48 h after a single resistance exercise bout, but not at post 1 h or after the 21-week resistance training period in untrained young men. On the other hand, UPR indicators were unchanged 1 and 2 days after a single sACVR administration. However, after 2 weeks of sACVR administration, which is a time-point when muscle growth had occurred, the UPR indicators HSP47, p-eIF2α and GRP78 increased (p<0.05). Conclusions. Resistance exercise/training and myostatin/activin blocking have different effects on skeletal muscle unfolded protein response even though both increase muscle protein synthesis and hypertrophy.

Where applicable, experiments conform with Society ethical requirements