Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids
Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids
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DOI：
10.1111/j.1432-1033.2004.04151.x
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发表时间：
2004-06-01
期刊：
影响因子：
--
通讯作者：
Saggerson, D
中科院分区：
文献类型：
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作者：
Clark, H;Carling, D;Saggerson, D
在大鼠心脏灌注5 mM葡萄糖（含或不含棕榈酸酯或油酸酯）1小时。脂肪酸的加入导致amp活化蛋白激酶(AMPK) α -1或α -2亚型的活性增加，乙酰辅酶a羧化酶的磷酸化增加，丙二酰辅酶a的组织含量降低。AMPK的激活不伴随着组织中ATP、ADP、AMP、磷酸肌酸或肌酸含量的变化。棕榈酸盐增加了AMPK α亚基中Thr172的磷酸化，并且棕榈酸盐对两种AMPK亚型的激活被蛋白磷酸酶2C消除，从而得出结论，暴露于脂肪酸会导致AMPK激酶的激活或AMPK磷酸酶的抑制。在体内，24小时的饥饿也增加了心脏AMPK活性和AMPK α亚基Thr172磷酸化。胰岛素灌注降低α -1和α -2 AMPK活性，增加丙二酰辅酶a含量。棕榈酸酯阻止了这两种影响。肾上腺素灌注降低丙二酰辅酶a含量，但不影响AMPK活性，但阻止棕榈酸活化AMPK。本文讨论了由未知脂肪酸驱动的信号过程激活AMPK的概念，为脂肪酸氧化的“前馈”激活提供了一种机制。
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 alpha-1 or the alpha-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 alpha-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 phosphatase. In vivo, 24 h of starvation also increased heart AMPK activity and Thr172 phosphorylation of AMPK alpha-subunits. Perfusion with insulin decreased both alpha-1 and alpha-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.