EXERCISE STIMULATES THE MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY IN HUMAN SKELETAL-MUSCLE

Physical exercise can cause marked alterations in the structure and fu nction of human skeletal muscle. However, little is known about the sp ecific signaling molecules and pathways that enable exercise to modula te cellular processes in skeletal muscle. The mitogen-activated protei n kinase (MAPK) cascade is a major signaling system by which cells tra nsduce extracellular signals into intracellular responses. We tested t he hypothesis that a single bout of exercise activates the MAPK signal ing pathway. Needle biopsies of vastus lateralis muscle were taken fro m nine subjects at rest and after 60 min of cycle ergometer exercise. In all subjects, exercise increased MAPK phosphorylation, and the acti vity of its downstream substrate, the p90 ribosomal S6 kinase 2. Furth ermore, exercise increased the activities of the upstream regulators o f MAPK, MAP kinase kinase, and Raf-1. When two additional subjects wer e studied using a one-legged exercise protocol, MAPK phosphorylation a nd p90 ribosomal S6 kinase 2, MAP kinase kinase 1, and Raf-1 activitie s were increased only in the exercising leg. These studies demonstrate that exercise activates the MAPK cascade in human skeletal muscle and that this stimulation is primarily a local, tissue-specific phenomeno n, rather than a systemic response to exercise. These findings suggest that the MAPK pathway may modulate cellular processes that occur in s keletal muscle in response to exercise.