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Involvement of AMPK in Alcohol Dehydrogenase Accentuated Myocardial Dysfunction Following Acute Ethanol Challenge in Mice.
- Source :
-
PLoS ONE . 2010, Vol. 5 Issue 6, p1-12. 12p. 1 Chart, 10 Graphs. - Publication Year :
- 2010
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Abstract
- Objectives: Binge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH) on ethanol-induced change in cardiac contractile function, intracellular Ca2+ homeostasis, insulin and AMPdependent kinase (AMPK) signaling. Methods: ADH transgenic and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Oral glucose tolerance test, cardiac AMP/ATP levels, cardiac contractile function, intracellular Ca2+ handling and AMPK signaling (including ACC and LKB1) were examined. Results: Ethanol exposure led to glucose intolerance, elevated plasma insulin, compromised cardiac contractile and intracellular Ca2+ properties, downregulated protein phosphatase PP2A subunit and PPAR-γ, as well as phosphorylation of AMPK, ACC and LKB1, all of which except plasma insulin were overtly accentuated by ADH transgene. Interestingly, myocardium from ethanol-treated FVB mice displayed enhanced expression of PP2Cα and PGC-1α, decreased insulin receptor expression as well as unchanged expression of Glut4, the response of which was unaffected by ADH. Cardiac AMPto- ATP ratio was significantly enhanced by ethanol exposure with a more pronounced increase in ADH mice. In addition, the AMPK inhibitor compound C (10 μM) abrogated acute ethanol exposure-elicited cardiomyocyte mechanical dysfunction. Conclusions: In summary, these data suggest that the ADH transgene exacerbated acute ethanol toxicity-induced myocardial contractile dysfunction, intracellular Ca2+ mishandling and glucose intolerance, indicating a role of ADH in acute ethanol toxicity-induced cardiac dysfunction possibly related to altered cellular fuel AMPK signaling cascade. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 52729892
- Full Text :
- https://doi.org/10.1371/journal.pone.0011268