NDLI: Apoptotic Cell Death in Cultured Cardiomyocytes Following Exposure to Low Concentrations of 4-Hydroxy-2-nonenal

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Apoptotic Cell Death in Cultured Cardiomyocytes Following Exposure to Low Concentrations of 4-Hydroxy-2-nonenal

Content Provider	Springer Nature Link
Author	Hortigón Vinagre, María P. Henao, Fernando
Copyright Year	2014
Abstract	Lipid peroxidation (LP), induced by oxidative stress, is associated with degenerative processes. 4-Hydroxy-2-nonenal (HNE), a highly reactive diffusible product of LP, is considered by-product and mediator of oxidative stress. Its level increases under pathological conditions such as cardiovascular diseases. In this study, we partially characterized the mechanisms of HNE-mediated cytotoxicity in cardiomyocytes. After establishing that pathophysiological doses of HNE trigger cell death dependent on the incubation time and dose of HNE (LD$_{50}$ = 4.4 μM), we tackled the mechanisms that underlie the cell death induced by HNE. Our results indicate that HNE rapidly increases intracellular Ca$^{2+}$; it also increases the rate of reactive oxygen species generation and causes a loss of mitochondrial membrane potential (ΔΨm) as well as a decrease in the ATP and GSH levels. Such alterations result in the activation of caspase-3 and DNA breakdown, both characteristic features of apoptotic cell death, as well as disruption of the cytoskeleton. Moreover, the nucleophilic compounds N-acetyl-cysteine and β-mercapto-propionyl-glycine, and the synthetic antioxidant Trolox exert a potent antioxidant action against HNE damage; this suggests its use as effective compounds in order to reduce the damage occurred as consequence of cardiovascular disorders in which oxidative stress and hence LP take place.
Starting Page	275
Ending Page	287
Page Count	13
File Format	PDF
ISSN	15307905
Journal	Cardiovascular Toxicology
Volume Number	14
Issue Number	3
e-ISSN	15590259
Language	English
Publisher	Springer US
Publisher Date	2014-03-11
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiomyocytes 4-Hydroxy-2-nonenal Calcium ROS Mitochondria Apoptosis Pharmacology/Toxicology Cardiology
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Toxicology Cardiology and Cardiovascular Medicine

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