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• W2034110828 startingPage "67" @default.
• W2034110828 abstract "Despite the high expression of 5′AMP activated protein kinase (AMPK) in heart, the activity and function of this enzyme in heart muscle has not been characterized. We demonstrate that rat hearts have a high AMPK activity, comparable to that found in liver, which could be stimulated up to 3-fold by 5′AMP. Cardiac AMPK is also under phosphorylation control, since in vitro incubation of cardiac AMPK with protein phosphatase 2A completely abolished activity, while incubation with ATP/Mg2+ resulted in over a 2-fold increase in activity. To investigate the function of AMPK in heart muscle, isolated working rat hearts were subjected to 30 min of global no-flow ischemia, followed by 60 min of aerobic reperfusion. AMPK activity was increased in heart at the end of reperfusion compared to aerobic controls (379±53 (n = 5) vs. 139±19 (n = 5) pmol·min−1· mg protein−1, P < 0.05, respectively). Treatment of AMPK in vitro with protein phosphatase 2A reversed this activation. Since AMPK can phosphorylate and inactivate acetyl-CoA carboxylase (ACC) in other tissues, and heart ACC has an important role in regulating fatty acid oxidation, we measured ACC activity in hearts reperfused post-ischemia. ACC activity was decreased at the end of reperfusion compared to aerobic controls (3.64±0.36 (n = 9) vs. 10.93±0.60 (n = 11) nmol· min−1· mg protein−1, respectively, P < 0.05). A significant negative correlation (r = −0.78) was observed between AMPK activity and ACC activity measured in aerobic and reperfused ischemic hearts. Low ACC activity could be reversed if ACC was extracted from hearts in the absence of phosphatase inhibitors, suggesting that phosphorylation of ACC decreased enzyme activity. This suggests that following ischemia AMPK is phosphorylated and activated (possibly by an AMPK kinase). AMPK then phosphorylates and inactivates ACC. The resultant decrease in malonyl-CoA levels could explain the acceleration of fatty acid oxidation that is observed during reperfusion of ischemic hearts." @default.
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• W2034110828 date "1996-05-01" @default.
• W2034110828 modified "2023-10-15" @default.
• W2034110828 title "Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia" @default.
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• W2034110828 doi "https://doi.org/10.1016/0005-2760(96)00013-6" @default.
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