Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 46, Issue 2, Pages 278-284Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2008.09.713
Keywords
PKC; Ethanol preconditioning; Mitochondria; In vivo; ALDH2; HNE; Oxidative stress; Stress signaling; Acute myocardial infarction; Ischemia/reperfusion; Ischemic preconditioning
Categories
Funding
- National Institutes of Health [NIH AA11147]
Ask authors/readers for more resources
The cardioprotective effects of moderate alcohol consumption have been well documented in animal models and in humans. Protection afforded against ischemia and reperfusion injury (I/R) proceeds through an ischemic preconditioning-like mechanism involving the activation of epsilon protein kinase C (epsilon PKC) and is dependent on the time and duration of ethanol treatment. However, the substrates of epsilon PKC and the molecular mechanisms by which the enzyme protects the heart from oxidative damage induced by I/R are not fully described. Using an open-chest model of acute myocardial infarction in vivo, we find that intraperitoneal injection of ethanol (0.5 g/kg) 60 min prior to (but not 15 min prior to) a 30-minute transient ligation of the left anterior descending coronary artery reduced I/R-mediated injury by 57% (measured as a decrease of creatine phosphokinase release into the blood). Only under cardioprotective conditions, ethanol treatment resulted in the translocation Of epsilon PKC to cardiac mitochondria, where the enzyme bound aldehyde dehydrogenase-2 (ALDH2). ALDH2 is an intra-mitochondrial enzyme involved in the detoxification of toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE) and 4-HNE mediates oxidative damage, at least in part, by covalently modifying and inactivating proteins (by forming 4-HNE adducts). In hearts subjected to I/R after ethanol treatment, the levels of 4-HNE protein adducts were lower and JNK1/2 and ERK1/2 activities were diminished relative to the hearts from rats subjected to I/R in the absence of ethanol. Together, this work provides an insight into the mitochondrial-dependent basis of ethanol-induced and epsilon PKC-mediated protection from cardiac ischemia, in vivo. (C) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available