Involvement of AMPK in alcohol dehydrogenase accentuated myocardial dysfunction following acute ethanol challenge in mice.
Involvement of AMPK in alcohol dehydrogenase accentuated myocardial dysfunction following acute ethanol challenge in mice.
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DOI：
10.1371/journal.pone.0011268
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发表时间：
2010-06-23
期刊：
影响因子：
3.7
通讯作者：
Ren J
中科院分区：
文献类型：
--
作者：
Guo R;Scott GI;Ren J
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 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 Ca2+ handling and AMPK signaling (including ACC and LKB1) were examined. 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 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 µM) 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 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.
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影响因子：
2.3
作者：
Ren, Jun;Wold, Loren E
通讯作者：
Wold, Loren E
影响因子：
37.8
作者：
Lamberts, Regis R.;Onderwater, Geert;Bouwman, R. Arthur
通讯作者：
Bouwman, R. Arthur
DOI：
10.1152/ajpheart.00780.2001
发表时间：
2002-04-01
影响因子：
4.8
作者：
Duan, JH;McFadden, GE;Ren, J
通讯作者：
Ren, J
影响因子：
24
作者：
Ma, Heng;Li, Ji;Ren, Jun
通讯作者：
Ren, Jun
影响因子：
3.7
作者：
Guo R;Ren J
通讯作者：
Ren J