Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise

J Physiol. 2003 Jan 15;546(Pt 2):327-35. doi: 10.1113/jphysiol.2002.034223.

Abstract

We determined whether mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signalling cascades are activated in response to intense exercise in skeletal muscle from six highly trained cyclists (peak O(2) uptake (.V(O2,peak)) 5.14 +/- 0.1 l min(-1)) and four control subjects (Vdot;(O(2))(,peak) 3.8 +/- 0.1 l min(-1)) matched for age and body mass. Trained subjects completed eight 5 min bouts of cycling at approximately 85% of .V(O2,peak) with 60 s recovery between work bouts. Control subjects performed four 5 min work bouts commencing at the same relative, but a lower absolute intensity, with a comparable rest interval. Vastus lateralis muscle biopsies were taken at rest and immediately after exercise. Extracellular regulated kinase (ERK1/2), p38 MAPK, histone H3, AMPK and acetyl CoA-carboxylase (ACC) phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activity of mitogen and stress-activated kinase 1 (MSK1; a substrate of ERK1/2 and p38 MAPK) and alpha(1) and alpha(2) subunits of AMPK were determined by immune complex assay. ERK1/2 and p38 MAPK phosphorylation and MSK1 activity increased (P < 0.05) after exercise 2.6-, 2.1- and 2.0-fold, respectively, in control subjects and 1.5-, 1.6- and 1.4-fold, respectively, in trained subjects. Phosphorylation of histone H3, a substrate of MSK1, increased (P < 0.05) approximately 1.8-fold in both control and trained subject. AMPKalpha(2) activity increased (P < 0.05) after exercise 4.2- and 2.3-fold in control and trained subjects, respectively, whereas AMPKalpha(1) activity was not altered. Exercise increased ACC phosphorylation (P < 0.05) 1.9- and 2.8-fold in control and trained subjects. In conclusion, intense cycling exercise in subjects with a prolonged history of endurance training increases MAPK signalling to the downstream targets MSK1 and histone H3 and isoform-specific AMPK signalling to ACC. Importantly, exercise-induced signalling responses were greater in untrained men, even at the same relative exercise intensity, suggesting muscle from previously well-trained individuals requires a greater stimulus to activate signal transduction via these pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase / metabolism
  • Adult
  • Bicycling* / physiology*
  • Histones / metabolism
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / metabolism*
  • Phosphorylation
  • Physical Endurance*
  • Protein Serine-Threonine Kinases / metabolism*
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Signal Transduction*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Histones
  • Multienzyme Complexes
  • PRKAA2 protein, human
  • Protein Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human
  • Acetyl-CoA Carboxylase