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

Authors

  • Mei Yu,

    1. Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
    2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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  • Eva Blomstrand,

    1. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    2. Department of Health and Sport Sciences, University College of Sports and Exercise, Stockholm, Sweden
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  • Alexander V. Chibalin,

    1. Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
    2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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  • Anna Krook,

    1. Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
    2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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  • Juleen R. Zierath

    Corresponding author
    1. Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
    2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    • Corresponding author
      J. R. Zierath: Department of Clinical Physiology and Integrative Physiology, Karolinska Institutet, von Eulers väg 4, II, SE-171 77 Stockholm, Sweden. Email: juleen.zierath@fyfa.ki.se

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Abstract

  • 1We 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.
  • 2Eleven 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.
  • 3Muscle 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.
  • 4In 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.

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