Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents
Détails
ID Serval
serval:BIB_E596C9C7C005
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents
Périodique
Biochemical Pharmacology
ISSN
0006-2952 (Print)
Statut éditorial
Publié
Date de publication
12/2002
Volume
64
Numéro
12
Pages
1785-91
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec 15
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec 15
Résumé
Reactive oxygen and nitrogen species are overproduced in the cardiovascular system during circulatory shock. Oxidant-induced cell injury involves the activation of poly(ADP-ribose) polymerase (PARP). Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the new potent phenanthridinone PARP inhibitor PJ34 [the hydrochloride salt of N-(oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide], we studied whether the impaired cardiac function in endotoxic shock is dependent upon the PARP pathway. Escherichia coli endotoxin (lipopolysaccharide, LPS) at 55 mg/kg, i.p., induced a severe depression of the systolic and diastolic contractile function, tachycardia, and a reduction in mean arterial blood pressure in both rats and mice. Treatment with PJ34 significantly improved cardiac function and increased the survival of rodents. In addition, LPS-induced depression of left ventricular performance was significantly less pronounced in PARP-1 knockout mice (PARP(-/-)) as compared with their wild-type littermates (PARP(+/+)). Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock.
Mots-clé
Animals
Death
Disease Models, Animal
Drug Interactions
Endotoxins/*toxicity
Enzyme Activation
Gene Deletion
Heart Diseases/chemically induced/*enzymology/mortality
Heart Function Tests
Lipopolysaccharides/pharmacology
Male
Mice
Phenanthrenes/pharmacology
Poly(ADP-ribose) Polymerases/antagonists & inhibitors/genetics/*physiology
Rats
Rats, Wistar
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
20/08/2019 17:08