title: Apoptotic cell death in cultured cardiomyocytes following exposure to low concentrations of 4-hydroxy-2-nonenal.
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 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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, 06071, Badajoz, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Hortigón-Vinagre
authors.forename: Fernando
authors.initials: F
authors.lastname: Henao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D066126:Cardiotoxicity / Q000473:pathology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D003599:Cytoskeleton / Q000473:pathology; D005434:Flow Cytometry; D015227:Lipid Peroxidation; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D002839:Chromans; D015853:Cysteine Proteinase Inhibitors; C027576:4-hydroxy-2-nonenal; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium; D000111:Acetylcysteine