Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle
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5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK a/ß/¿-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)ß. Also, exercise training decreases expression of the regulatory ¿3 AMPK subunit and attenuates a2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK heterotrimers. We provide evidence here that only the a2/ß2/¿3 subunit is phosphorylated and activated during high-intensity exercise in vivo. The activity associated with the remaining two AMPK heterotrimers, a1/ß2/¿1 and a2/ß2/¿1, is either unchanged (20 min, 80% maximal oxygen uptake (VO2,peak)) or decreased (30 or 120 s sprint-exercise). The differential activity of the heterotrimers leads to a total a-AMPK activity, that is decreased (30 s trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity associated with the a2/ß2/¿3 heterotrimer was strongly correlated to ¿3-associated a-Thr-172 AMPK phosphorylation (r2 = 0.84, P < 0.001) and to ACCß Ser-221 phosphorylation (r2 = 0.65, P < 0.001). These data single out the a2/ß2/¿3 heterotrimer as an important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCß.
|Tidsskrift||Journal of Physiology|
|Status||Udgivet - 2006|
PUF 2006 5200 156