Homocysteine Induces Cell Death in H9c2 Cardiomyocytes Through the Generation of Peroxynitrite.
From: Department of Intensive Care Medicine, University Hospital Center, 1011 Lausanne, Switzerland.
Biochemical and biophysical research communications
- Publish Date: Aug 2007
- ISSN: 0006-291X
- Volume: 359
- Issue: 3
- Pages: 445-50
- Medium: Print
- Language: English
- Citation (JAMA): Levrand Sandra, Pacher Pal, Pesse Benoît, et al. Homocysteine Induces Cell Death in H9c2 Cardiomyocytes Through the Generation of Peroxynitrite.. Biochem. Biophys. Res. Commun. Aug 2007;359:445-50
Abstract
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.
Mesh Headings (Keywords): Animals, Apoptosis, Caspase 3, Catalysis, Cells, Cultured, Cytoprotection, Extracellular Signal-Regulated MAP Kinases, Homocystine, JNK Mitogen-Activated Protein Kinases, L-Lactate Dehydrogenase, Metalloporphyrins, Myocytes, Cardiac, Necrosis, Peroxynitrous Acid, Phosphorylation, Poly(ADP-ribose) Polymerases, Rats
Check for Full Text / PubMed Unique Identifier (PMID): 17544363
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.