5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle.
The 5'-AMP-activated protein kinase (AMPK) is proposed to be involved in signaling pathways leading to adaptations in skeletal muscle in response to both a single exercise bout and exercise training. This study investigated the effect of endurance training on protein content of catalytic (alpha1, alpha2) and regulatory (beta1, beta2 and gamma1, gamma2, gamma3) subunit isoforms of AMPK as well as on basal AMPK activity in human skeletal muscle. Eight healthy young men performed supervised one-legged knee extensor endurance training for 3 wk. Muscle biopsies were obtained before and 15 h after training in both legs. In response to training the protein content of alpha1, beta2 and gamma1 increased in the trained leg by 41, 34, and 26%, respectively (alpha1 and beta2 P < 0.005, gamma1 P < 0.05). In contrast, the protein content of the regulatory gamma3-isoform decreased by 62% in the trained leg (P = 0.01), whereas no effect of training was seen for alpha2, beta1, and gamma2. AMPK activity associated with the alpha1- and the alpha2-isoforms increased in the trained leg by 94 and 49%, respectively (both P < 0.005). In agreement with these observations, phosphorylation of alpha-AMPK-(Thr172) and of the AMPK target acetyl-CoA carboxylase-beta(Ser221) increased by 74 and 180%, respectively (both P < 0.001). Essentially similar results were obtained in four additional subjects studied 55 h after training. This study demonstrates that protein content and basal AMPK activity in human skeletal muscle are highly susceptible to endurance exercise training. Except for the increase in gamma1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contralateral untrained muscle.
Frøsig
Christian
C
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. Cfrosig@ifi.ku.dk
Jørgensen
Sebastian B
SB
Hardie
D Grahame
DG
Richter
Erik A
EA
Wojtaszewski
Jørgen F P
JF
D055372:AMP-Activated Protein Kinases; D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D004789:Enzyme Activation; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007717:Knee / Q000502:physiology; D008297:Male; D009097:Multienzyme Complexes / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D010806:Physical Education and Training / Q000379:methods*; D010807:Physical Endurance / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D009097:Multienzyme Complexes; C526181:PRKAA2 protein, human; C526182:PRKAB1 protein, human; C526183:PRKAB2 protein, human; C526222:PRKAG1 protein, human; C526225:PRKAG3 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human