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

• Published in: The Journal of physiology Vol. 546; no. 2; pp. 327 - 335
• Main Authors: Yu, Mei, Stepto, Nigel K., Chibalin, Alexander V., Fryer, Lee G. D., Carling, Dave, Krook, Anna, Hawley, John A., Zierath, Juleen R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 15.01.2003; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Acetyl-CoA Carboxylase - metabolism; Adult; AMP-Activated Protein Kinases; 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; Original; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Physical Endurance; Protein-Serine-Threonine Kinases - metabolism; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; Signal Transduction
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2002.034223

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 ( ) 5.14 ± 0.1 l min −1 ) and four control subjects ( 3.8 ± 0.1 l min −1 ) matched for age and body mass. Trained subjects completed eight 5 min bouts of cycling at ≈85% of 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 α 1 and α 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) ≈1.8-fold in both control and trained subject. AMPKα 2 activity increased ( P < 0.05) after exercise 4.2- and 2.3-fold in control and trained subjects, respectively, whereas AMPKα 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.