Peroxynitrite induces HMGB1 release by cardiac cells in vitro and HMGB1 upregulation in the infarcted myocardium in vivo.

Détails

Ressource 1Télécharger: serval:BIB_61E119D8C3E2.P001 (490.78 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
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ID Serval
serval:BIB_61E119D8C3E2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Peroxynitrite induces HMGB1 release by cardiac cells in vitro and HMGB1 upregulation in the infarcted myocardium in vivo.
Périodique
Cardiovascular Research
Auteur(s)
Loukili N., Rosenblatt-Velin N., Li J., Clerc S., Pacher P., Feihl F., Waeber B., Liaudet L.
ISSN
1755-3245[electronic], 0008-6363[linking]
Statut éditorial
Publié
Date de publication
2011
Volume
89
Numéro
3
Pages
586-594
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
AIMS: High-mobility group box 1 (HMGB1) is a nuclear protein actively secreted by immune cells and passively released by necrotic cells that initiates pro-inflammatory signalling through binding to the receptor for advance glycation end-products. HMGB1 has been established as a key inflammatory mediator during myocardial infarction, but the proximal mechanisms responsible for myocardial HMGB1 expression and release in this setting remain unclear. Here, we investigated the possible involvement of peroxynitrite, a potent cytotoxic oxidant formed during myocardial infarction, on these processes. METHODS AND RESULTS: The ability of peroxynitrite to induce necrosis and HMGB1 release in vitro was evaluated in H9c2 cardiomyoblasts and in primary murine cardiac cells (myocytes and non-myocytes). In vivo, myocardial HMGB1 expression and nitrotyrosine content (a marker of peroxynitrite generation) were determined following myocardial ischaemia and reperfusion in rats, whereas peroxynitrite formation was inhibited by two different peroxynitrite decomposition catalysts: 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (III) (FeTPPS) or Mn(III)-tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP). In all types of cells studied, peroxynitrite (100 μM) elicited significant necrosis, the loss of intracellular HMGB1, and its passive release into the medium. In vivo, myocardial ischaemia-reperfusion induced significant myocardial necrosis, cardiac nitrotyrosine formation, and marked overexpression of myocardial HMGB1. FeTPPS reduced nitrotyrosine, decreased infarct size, and suppressed HMGB1 overexpression, an effect that was similarly obtained with MnTBAP. CONCLUSION: These findings indicate that peroxynitrite represents a key mediator of HMGB1 overexpression and release by cardiac cells and provide a novel mechanism linking myocardial oxidative/nitrosative stress with post-infarction myocardial inflammation.
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/12/2010 10:11
Dernière modification de la notice
25/09/2019 7:09
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