Involvement of AMPK in Alcohol Dehydrogenase Accentuated Myocardial Dysfunction Following Acute Ethanol Challenge in Mice

摘要: OBJECTIVES Binge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine impact of cardiac-specific overexpression dehydrogenase (ADH) on ethanol-induced change in cardiac function, intracellular Ca(2+) homeostasis, insulin and AMP-dependent kinase (AMPK) signaling. METHODS ADH transgenic wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Oral glucose tolerance test, AMP/ATP levels, handling AMPK signaling (including ACC LKB1) examined. RESULTS Ethanol exposure led intolerance, elevated plasma insulin, compromised properties, downregulated protein phosphatase PP2A subunit PPAR-gamma, as well phosphorylation AMPK, LKB1, all which except overtly accentuated by transgene. Interestingly, myocardium from ethanol-treated displayed enhanced expression PP2Calpha PGC-1alpha, decreased receptor unchanged Glut4, response unaffected ADH. Cardiac AMP-to-ATP ratio significantly a more pronounced increase mice. In addition, inhibitor compound C (10 microM) abrogated acute exposure-elicited cardiomyocyte mechanical dysfunction. CONCLUSIONS summary, these data suggest that transgene exacerbated toxicity-induced dysfunction, mishandling indicating role possibly related altered cellular fuel cascade.