Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type.
Protein synthesis in skeletal muscle is known to decrease during exercise, and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) phosphorylation, key components in the mRNA translation machinery, were examined together with AMP-activated protein kinase (AMPK) in healthy young men. Skeletal muscle eEF2 phosphorylation at Thr56 increased during exercise but was not influenced by exercise intensity, and was lower than rest 30 min after exercise. On the other hand, 4EBP1 phosphorylation at Thr37/46 decreased during exercise, and this decrease was greater at higher exercise intensities and was similar to rest 30 min after exercise. AMPK activity, as indexed by AMPK alpha-subunit phosphorylation at Thr172 and phosphorylation of the AMPK substrate ACCbeta at Ser221, was higher with higher exercise intensities, and these indices were higher than rest after high-intensity exercise only. Using immunohistochemistry, it was shown that the increase in skeletal muscle eEF2 Thr56 phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e., 4EBP1) and elongation (i.e., eEF2) steps, with eEF2 phosphorylation contributing at all exercise intensities but 4EBP1 dephosphorylation contributing to a greater extent at high vs. low exercise intensities.
Rose
Adam J
AJ
Molecular Physiology Group, Copenhagen Muscle Research Centre, Dept. of Exercise and Sport Sciences, Section of Human Physiology, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark, 2100. arose@ifi.ku.dk
Bisiani
Bruno
B
Vistisen
Bodil
B
Kiens
Bente
B
Richter
Erik A
EA
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D001642:Bicycling; D018797:Cell Cycle Proteins; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000378:metabolism*; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010807:Physical Endurance; D014176:Protein Biosynthesis; D015398:Signal Transduction; D013912:Threonine; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D020652:Peptide Elongation Factor 2; D010750:Phosphoproteins; D013912:Threonine; D055372:AMP-Activated Protein Kinases; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase