Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream targets in human skeletal muscle

Abstract

We tested the hypothesis that long‐distance running activates parallel mitogen‐activated protein kinase (MAPK) cascades that involve extracellular signal regulated kinase 1 and 2 (ERK1/2) and p38 MAPK and their downstream substrates. Eleven men completed a 42.2 km marathon (mean race time 4 h 1 min; range 2 h 56 min to 4 h 33 min). Vastus lateralis muscle biopsies were obtained before and after the race. Glycogen content was measured spectrophotometrically. ERK1/2 and p38 MAPK phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activation of the downstream targets of ERK1/2 and p38 MAPK, MAPK‐activated protein kinase‐1 (MAPKAP‐K1; also called p90 ribosomal S6 kinase, p90rsk), MAPK‐activated protein kinase‐2 (MAPKAP‐K2), mitogen‐ and stress‐activated kinase 1 (MSK1) and mitogen‐ and stress‐activated kinase 2 (MSK2) was determined using immune complex assays. Muscle glycogen content was reduced by 40 ± 6 % after the marathon. ERK1/2 phosphorylation increased 7.8‐fold and p38 MAPK phosphorylation increased 4.4‐fold post‐exercise. Prolonged running did not alter ERK1/2 and p38 MAPK protein expression. The activity of p90rsk, a downstream target of ERK1/2, increased 2.8‐fold after the marathon. The activity of MAPKAPK‐K2, a downstream target of p38 MAPK, increased 3.1‐fold post‐exercise. MSK1 and MSK2 are downstream of both ERK1/2 and p38 MAPK. MSK1 activity increased 2.4‐fold post‐exercise. MSK2 activity was low, relative to MSK1, with little activation post‐exercise. In conclusion, prolonged distance running activates MAPK signalling cascades in skeletal muscle, including increased activity of downstream targets: p90rsk, MAPKAP‐K2 and MSK. Activation of these downstream targets provides a potential mechanism by which exercise induces gene transcription in skeletal muscle.

Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle: effects of high-fat diet and exercise

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Plasma cytokine response, lipid peroxidation and NF-κB activation in skeletal muscle following maximum progressive swimming

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Exercise and Myocyte Enhancer Factor 2 Regulation in Human Skeletal Muscle

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