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Involvement of AMPK in alcohol dehydrogenase accentuated myocardial dysfunction following acute ethanol challenge in mice.
- Source :
- PLoS ONE, Vol 5, Iss 6, p e11268 (2010)
- Publication Year :
- 2010
- Publisher :
- Public Library of Science (PLoS), 2010.
-
Abstract
- 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 Ca(2+) homeostasis, insulin and AMP-dependent kinase (AMPK) signaling.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 Ca(2+) handling and AMPK signaling (including ACC and LKB1) were examined.Ethanol exposure led to glucose intolerance, elevated plasma insulin, compromised cardiac contractile and intracellular Ca(2+) properties, downregulated protein phosphatase PP2A subunit and PPAR-gamma, 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 PP2Calpha and PGC-1alpha, decreased insulin receptor expression as well as unchanged expression of Glut4, the response of which was unaffected by ADH. Cardiac AMP-to-ATP ratio was significantly enhanced by ethanol exposure with a more pronounced increase in ADH mice. In addition, the AMPK inhibitor compound C (10 microM) abrogated acute ethanol exposure-elicited cardiomyocyte mechanical dysfunction.In summary, these data suggest that the ADH transgene exacerbated acute ethanol toxicity-induced myocardial contractile dysfunction, intracellular Ca(2+) 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.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5ab9a5a25d944acbbb21f35bb8b2b78d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0011268