Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation
Détails
ID Serval
serval:BIB_BB39A2E79F82
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation
Périodique
Nature Medicine
ISSN
1078-8956 (Print)
Statut éditorial
Publié
Date de publication
01/2001
Volume
7
Numéro
1
Pages
108-13
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Résumé
Diabetic patients frequently suffer from retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. The loss of endothelial function precedes these vascular alterations. Here we report that activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of endothelial dysfunction in diabetes. Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation. Treatment with a novel potent PARP inhibitor, starting after the time of islet destruction, maintained normal vascular responsiveness, despite the persistence of severe hyperglycemia. Endothelial cells incubated in high glucose exhibited production of reactive nitrogen and oxygen species, consequent single-strand DNA breakage, PARP activation and associated metabolic and functional impairment. Basal and high-glucose-induced nuclear factor-kappaB activation were suppressed in the PARP-deficient cells. Our results indicate that PARP may be a novel drug target for the therapy of diabetic endothelial dysfunction.
Mots-clé
Animals
Diabetes Mellitus, Experimental/enzymology/*physiopathology
Endothelium, Vascular/enzymology/*physiopathology
Enzyme Activation
Glucose/pharmacology
Immunohistochemistry
Mice
NF-kappa B/metabolism
Poly(ADP-ribose) Polymerases/*metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
20/08/2019 16:29