Contractions induce phosphorylation of the AMPK site Ser565 in hormone-sensitive lipase in muscle.
Intramyocellular triglyceride is an important energy store which is related to insulin resistance. Mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by epinephrine via PKA and by contractions via PKC and ERK. 5' AMP-activated protein kinase (AMPK) is an intracellular fuel gauge which regulates metabolism. In this study we incubated rat soleus muscle to investigate if AMPK influences HSL during 5min of repeated tetanic contractions. An eightfold increase in AMPK activity was accompanied by a 2.5-fold increase in phosphorylation of the AMPK-site Ser(565) in HSL (p<0.05). Inhibition of PKC by Calphostin C abolished the contraction-mediated HSL activation while HSL-Ser(565) phosphorylation was not reduced. The study indicates that during contractions AMPK phosphorylates HSL in Ser(565), but this phosphorylation is not directly responsible for the contraction-induced activation of HSL.
Donsmark
Morten
M
Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark. mdonsmark@mfi.ku.dk
Langfort
Jozef
J
Holm
Cecilia
C
Ploug
Thorkil
T
Galbo
Henrik
H
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D004837:Epinephrine / Q000737:chemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000737:chemistry*; D002787:Sterol Esterase / Q000737:chemistry*; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry
D009097:Multienzyme Complexes; D009281:Naphthalenes; D014280:Triglycerides; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D002787:Sterol Esterase; C058819:calphostin C; D004837:Epinephrine