Myocardial ischemic preconditioning in rodents is dependent on poly (ADP-ribose) synthetase

Détails

ID Serval
serval:BIB_337118F05C7A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Myocardial ischemic preconditioning in rodents is dependent on poly (ADP-ribose) synthetase
Périodique
Molecular Medicine
Auteur(s)
Liaudet  L., Yang  Z., Al-Affar  E. B., Szabo  C.
ISSN
1076-1551 (Print)
Statut éditorial
Publié
Date de publication
06/2001
Volume
7
Numéro
6
Pages
406-17
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun
Résumé
BACKGROUND: Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) in response to oxidant-mediated DNA injury has been shown to play an important role in the pathogenesis of reperfusion injury. Here we investigated the role of PARS in myocardial ischemic preconditioning (IPC). MATERIALS AND METHODS: Mice with or without genetic disruption of PARS and rats in the absence or presence of the PARS inhibitor 3-aminobenzamide underwent coronary occlusion and reperfusion with or without IPC. RESULTS: Both poly(ADP-ribose) synthetase (PARS) deficiency and ischemic preconditioning (IPC) induced protection from reperfusion injury, attenuated inflammatory mediator production, and reduced neutrophil infiltration when compared to the response in wild-type mice. Surprisingly, the protective effect of IPC not only disappeared in PARS-/- mice, but the degree of myocardial injury and inflammatory response was similar to the one seen in wild-type animals. Similarly, in the rat model of IPC, 3-aminobenzamide pretreatment blocked the beneficial effect of IPC. Myocardial NAD+ levels were maintained in the PARS-deficient mice during reperfusion, while depleted in the wild-type mice. The protection against reperfusion injury by IPC was also associated with partially preserved myocardial NAD+ levels, indicating that PARS activation is attenuated by IPC. This conclusion was further strengthened by poly(ADP-ribose) immunohistochemical measurements, demonstrating that IPC markedly inhibits PARS activation during reperfusion. CONCLUSIONS: The mode of IPC's action is related, at least in part, to an inhibition of PARS. This process may occur either by self-auto-ribosylation of PARS during IPC, and/or via the release of endogenous purines during IPC that inhibit PARS activation during reperfusion.
Mots-clé
Animals Benzamides/pharmacology Enzyme Inhibitors/pharmacology Immunohistochemistry Interleukin-10/blood Interleukin-12/blood *Ischemic Preconditioning, Myocardial Male Mice Mice, Knockout Myocardial Reperfusion Injury/enzymology/metabolism/pathology/*prevention & control Myocardium/*enzymology/metabolism/pathology NAD/metabolism Peroxidase/metabolism Poly(ADP-ribose) Polymerases/antagonists & inhibitors/genetics/*metabolism Rats Rats, Wistar Tissue Extracts Tumor Necrosis Factor-alpha/metabolism Tyrosine/*analogs & derivatives/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
03/03/2018 15:48
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