Repeated bouts of resistance exercise attenuate mitogen-activated protein-kinase signal responses in rat skeletal muscle

Resistance exercise training induces skeletal muscle hypertrophy, but repeated bouts gradually attenuate this anabolic effect. Attenuation of mechanistic target of rapamycin complex 1 (mTORC1) activation by repetitive resistance exercise is involved in this process, but the mechanism leading to inactivation of mTORC1 remains unclear. In this study, we investigated repetition-dependent changes in mitogen-activated protein kinases (MAPKs) and the 90-kDa ribosomal S6 kinase (p90RSK), upstream regulators of mTORC1, in a rat resistance-exercise model. Resistance exercise was associated with increased phosphorylation of 70-kDa ribosomal protein S6 kinase (Thr389), but its magnitude was decreased with repeated bouts. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204) and p38 MAPK (Thr180/Tyr182), which are MAPKs, decreased with repeated bouts. A similar result was also observed for p90RSK phosphorylation (Thr573). These observations indicate that repeated bouts desensitized ERK1/2 and p38 MAPK, subsequently attenuating p90RSK phosphorylation. This reduction in p90RSK phosphorylation may have been partly responsible for the blunting of mTORC1 activation by resistance exercise. (C) 2019 Published by Elsevier Inc.