Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of peroxynitrite

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_3E8465E67BE4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of peroxynitrite
Périodique
Biochemical and Biophysical Research Communications
Auteur(s)
Levrand S., Pacher P., Pesse B., Rolli J., Feihl F., Waeber B., Liaudet L.
ISSN
0006-291X (Print)
Statut éditorial
Publié
Date de publication
08/2007
Peer-reviewed
Oui
Volume
359
Numéro
3
Pages
445-50
Langue
anglais
Notes
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't --- Old month value: Aug 3
Résumé
Homocysteine (HCY) is toxic on blood vessels, but a potential direct toxicity of HCY on the heart is unknown. We addressed this issue by exposing H9C2 cardiomyocytes to HCY (0.1-5 mM) for up to 6h. At these concentrations, HCY reduced cell viability, induced necrosis and apoptosis and triggered the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP). This was associated with the intracellular generation of the potent oxidant peroxynitrite. Removing peroxynitrite by the decomposition catalyst FeTPPS considerably reduced LDH release, DNA fragmentation, cleavage of caspase-3 and PARP, and restored normal cell morphology. In additional experiments performed in primary rat ventricular cardiomyocytes, HCY (1 mM, 6h) activated the phosphorylation of the MAP kinases ERK and JNK, two essential stress signaling kinases regulating myocardial apoptosis, hypertrophy and remodeling. These results provide the first demonstration that HCY kills cardiomyocytes through the generation of peroxynitrite and can activate key signaling cascades in the myocardium.
Mots-clé
Animals Apoptosis/*drug effects Caspase 3/metabolism Catalysis Cells, Cultured Cytoprotection/drug effects Extracellular Signal-Regulated MAP Kinases/metabolism Homocystine/*toxicity JNK Mitogen-Activated Protein Kinases/metabolism L-Lactate Dehydrogenase/metabolism/secretion Metalloporphyrins/pharmacology Myocytes, Cardiac/*cytology/drug effects/*metabolism Necrosis/chemically induced/metabolism/pathology Peroxynitrous Acid/*biosynthesis Phosphorylation/drug effects Poly(ADP-ribose) Polymerases/metabolism Rats
Pubmed
Web of science
Création de la notice
25/01/2008 10:38
Dernière modification de la notice
20/08/2019 14:35
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