TAILIEUCHUNG - Báo cáo khoa học: Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids

Rat hearts were perfused for 1 h with 5 mMglucose with or without palmitate or oleate at concentrations characteristic of the fasting state. The inclusion of fatty acids resulted in increased activities of the a-1 or thea-2 isoforms of AMP-activated protein kinase (AMPK), increased phosphoryla-tion of acetyl-CoA carboxylase and a decrease in the tissue content of malonyl-CoA. Activation of AMPK was not accompanied by any changes in the tissue contents of ATP, ADP, AMP, phosphocreatine or creatine. . | Eur. J. Biochem. 1-10 2004 FEBS 2004 doi Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids Hilary Clark1 David Carling2 and David Saggerson1 1 Department of Biochemistry and Molecular Biology University College London UK 2Cellular Stress Group MRC Clinical Sciences Centre Imperial College School of Medicine Hammersmith Hospital London UK Rat hearts were perfused for 1 h with 5 mM glucose with or without palmitate or oleate at concentrations characteristic of the fasting state. The inclusion of fatty acids resulted in increased activities of the a-1 or the a-2 isoforms of AMP-activated protein kinase AMPK increased phosphorylation of acetyl-CoA carboxylase and a decrease in the tissue content of malonyl-CoA. Activation of AMPK was not accompanied by any changes in the tissue contents of ATP ADP AMP phosphocreatine or creatine. Palmitate increased phosphorylation of Thr172 within AMPK a-subunits and the activation by palmitate of both AMPK isoforms was abolished by protein phosphatase 2C leading to the conclusion that exposure to fatty acid caused activation of an AMPK kinase or inhibition of an AMPK phos phatase. In vivo 24 h of starvation also increased heart AMPK activity and Thr172 phosphorylation of AMPK a-subunits. Perfusion with insulin decreased both a-1 and a-2 AMPK activities and increased malonyl-CoA content. Palmitate prevented both of these effects. Perfusion with epinephrine decreased malonyl-CoA content without an effect on AMPK activity but prevented the activation of AMPK by palmitate. The concept is discussed that activation of AMPK by an unknown fatty acid-driven signalling process provides a mechanism for a feed-forward activation of fatty acid oxidation. Keywords AMP-activated protein kinase fatty acids heart insulin protein phosphorylation. The AMP-activated protein kinase AMPK is a heterotrimeric enzyme complex with a key role in the .

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