Apoptotic cell death in cultured cardiomyocytes following exposure to low concentrations of 4-hydroxy-2-nonenal

Hortigon-Vinagre, M. and Henao, F. (2014) Apoptotic cell death in cultured cardiomyocytes following exposure to low concentrations of 4-hydroxy-2-nonenal. Cardiovascular Toxicology, 14(3), pp. 275-287. (doi: 10.1007/s12012-014-9251-5) (PMID:24615591)

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 (LD50 = 4.4 μM), we tackled the mechanisms that underlie the cell death induced by HNE. Our results indicate that HNE rapidly increases intracellular Ca2+; 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hortigon, Dr Maria
• Authors: Hortigon-Vinagre, M., and Henao, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cardiovascular Toxicology
• Publisher: Springer
• ISSN: 1530-7905
• ISSN (Online): 1559-0259