Article

Alpha lipoic acid protects heart against myocardial ischemia-reperfusion injury through a mechanism involving aldehyde dehydrogenase 2 activation.

Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
European journal of pharmacology (impact factor: 2.59). 03/2012; 678(1-3):32-8. DOI:10.1016/j.ejphar.2011.12.042 pp.32-8
Source: PubMed

ABSTRACT Recent studies demonstrate that alpha lipoic acid can prevent nitroglycerin tolerance by restoring aldehyde dehydrogenase 2 (ALDH2) activity and ALDH2-mediated detoxification of aldehydes is thought as an endogenous mechanism against ischemia-reperfusion injury. This study was performed to explore whether the cardioprotective effect of alpha lipoic acid was related to activation of ALDH2 and the underlying mechanisms. In a Langendorff model of ischemia-reperfusion in rats, cardiac function, activities of creatine kinase (CK) and ALDH2, contents of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. In a cell model of hypoxia-reoxygenation, the apoptosis, ALDH activity, reactive oxygen species level, 4-HNE and MDA contents were examined. In the isolated hearts, ischemia-reperfusion treatment led to cardiac dysfunction accompanied by an increase in 4-HNE and MDA contents. Pretreatment with lipoic acid significantly up-regulated myocardial ALDH2 activity concomitantly with an improvement of cardiac dysfunction and a decrease in 4-HNE and MDA contents, these effects were blocked by the inhibitor of ALDH2. Similarly, in the cultured cardiomyocytes, hypoxia-reoxygenation treatment induced apoptosis accompanied by an increase in the production of reactive oxygen species, 4-HNE and MDA. Administration of lipoic acid significantly up-regulated cellular ALDH2 activity concomitantly with a reduction in apoptosis, production of reactive oxygen species, 4-HNE and MDA, these effects were reversed in the presence of ALDH2 or PKCε inhibitors. Our results suggest that the cardioprotective effects of lipoic acid on ischemia-reperfusion injury are through a mechanism involving ALDH2 activation. The regulatory effect of lipoic acid on ALDH2 activity is dependent on PKCε signaling pathway.

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    Article: Mitochondria as a drug target in ischemic heart disease and cardiomyopathy.
    Andrew M Walters, George A Porter, Paul S Brookes
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

aldehyde dehydrogenase 2
 
ALDH2 activation
 
ALDH2 activity
 
ALDH2-mediated detoxification
 
alpha lipoic acid
 
cardiac dysfunction
 
cardiac function
 
cardioprotective effects
 
cell model
 
creatine kinase
 
endogenous mechanism
 
hypoxia-reoxygenation treatment induced apoptosis
 
ischemia-reperfusion treatment
 
Langendorff model
 
PKCε inhibitors
 
PKCε signaling pathway
 
Pretreatment
 
reactive oxygen species
 
reactive oxygen species level
 
underlying mechanisms