Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines.

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_13E8AB10D0AC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines.
Périodique
Journal of Biological Chemistry
Auteur(s)
Levrand S., Pesse B., Feihl F., Waeber B., Pacher P., Rolli J., Schaller M.D., Liaudet L.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
10/2005
Peer-reviewed
Oui
Volume
280
Numéro
41
Pages
34878-34887
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Peroxynitrite is a potent oxidant and nitrating species proposed as a direct effector of myocardial damage in numerous cardiac pathologies. Whether peroxynitrite also acts indirectly, by modulating cell signal transduction in the myocardium, has not been investigated. Therefore, we examined a possible role for peroxynitrite on the activation of NF-kappaB, a crucial pro-inflammatory transcription factor, in cultured H9C2 cardiomyocytes. H9C2 cells were stimulated with tumor necrosis factor-alpha or lipopolysaccharide following a brief (20-min) exposure to peroxynitrite. NF-kappaB activation (phosphorylation and degradation of its inhibitor IkappaBalpha, nuclear translocation of NF-kappaB p65, and NF-kappaB DNA binding) triggered by lipopolysaccharide or tumor necrosis factor-alpha was abrogated by peroxynitrite. Peroxynitrite also inhibited NF-kappaB in two human endothelial cell lines activated with tumor necrosis factor-alpha or interleukin-1beta. These effects were related to oxidative but not nitrative chemistry and were still being observed while nitration was suppressed by epicatechin. The mechanism of NF-kappaB inhibition by peroxynitrite was a complete blockade of phosphorylation and activation of the upstream kinase IkappaB kinase (IKK) beta, required for canonical, pro-inflammatory NF-kappaB activation. At the same time, peroxynitrite activated phosphorylation of NF-kappaB-inducing kinase and IKKalpha, considered as part of an alternative, noncanonical NF-kappaB activation pathway. Suppression of IKKbeta-dependent NF-kappaB activation translated into a marked inhibition of the transcription of NF-kappaB-dependent genes by peroxynitrite. Thus, peroxynitrite has a dual effect on NF-kappaB, inhibiting canonical IKKbeta-dependent NF-kappaB activation while activating NF-kappaB-inducing kinase and IKKalpha phosphorylation, which suggests its involvement in an alternative pathway of NF-kappaB activation. These findings offer new perspectives for the understanding of the relationships between redox stress and inflammation.
Mots-clé
Active Transport, Cell Nucleus, Animals, Blotting, Western, Cell Line, Cell Nucleus/metabolism, Cell Survival, Cytoplasm/metabolism, Electrophoresis, Polyacrylamide Gel, Endothelial Cells/cytology, Genes, Reporter, Immunohistochemistry, Immunoprecipitation, Inflammation, Interleukin-1/metabolism, Lipopolysaccharides/chemistry, Lipopolysaccharides/metabolism, Luciferases/metabolism, Models, Biological, Myocardium/cytology, NF-kappa B/chemistry, NF-kappa B/metabolism, Oxidation-Reduction, Oxygen/metabolism, Peroxynitrous Acid/chemistry, Peroxynitrous Acid/metabolism, Phosphorylation, Rats, Signal Transduction, Tetrazolium Salts/pharmacology, Thiazoles/pharmacology, Time Factors, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 10:38
Dernière modification de la notice
03/03/2018 14:03
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