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Titolo:
Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly (ADP-ribose) polymerase activation
Autore:
Soriano, FG; Virag, L; Szabo, C;
Indirizzi:
Inotek Corp, Beverly, MA 01915 USA Inotek Corp Beverly MA USA 01915Inotek Corp, Beverly, MA 01915 USA Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA Univ Med & Dent New Jersey Newark NJ USA 07103 Surg, Newark, NJ 07103 USA Debrecen Univ Med, Dept Med Chem, H-4012 Debrecen, Hungary Debrecen Univ Med Debrecen Hungary H-4012 Chem, H-4012 Debrecen, Hungary
Titolo Testata:
JOURNAL OF MOLECULAR MEDICINE-JMM
fascicolo: 8, volume: 79, anno: 2001,
pagine: 437 - 448
SICI:
0946-2716(200108)79:8<437:DEDROR>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; POLY(ADENOSINE DIPHOSPHATE RIBOSE); INTERCELLULAR-ADHESION MOLECULE-1; CELLULAR-ENERGY DEPLETION; DNA STRAND BREAKAGE; POLY(ADP-RIBOSE) POLYMERASE; OXIDATIVE STRESS; GENE-TRANSCRIPTION; ENDOTOXIC-SHOCK;
Keywords:
free radicals; oxidants; nitric oxide; diabetes vascular; cytokine;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
92
Recensione:
Indirizzi per estratti:
Indirizzo: Szabo, C Inotek Corp, Suite 419E,100 Cummings Ctr, Beverly, MA 01915 USA Inotek Corp Suite 419E,100 Cummings Ctr Beverly MA USA 01915 USA
Citazione:
F.G. Soriano et al., "Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly (ADP-ribose) polymerase activation", J MOL MED-J, 79(8), 2001, pp. 437-448

Abstract

Peroxynitrite and hydroxyl radicals are potent initiators of DNA single-strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP ribose) polymerase (PARP). In response to high glucose incubation medium in vitro, or diabetes and hyperglycemia in vivo, reactive nitrogen and oxygen species generation occurs. These reactive species trigger DNA single-strand breakage, which induces rapid activation of PARP. PARP in turn depletes the intracellular concentration of its substrate, NAD(), slowing the rate of glycolysis, electron transport, and ATP formation. This process results in acute endothelial dysfunction in diabetic blood vessels. Accordingly, inhibitors of PARP protect against endothelial injury under these conditions. In addition to the direct cytotoxic pathway regulatedby DNA injury and PARP activation, PARP also appears to modulate the course of inflammation by regulating the activation of nuclear factor kappaB, and the expression of a number of genes, including the gene for intercellularadhesion molecule I and the inducible nitric oxide synthase. The research into the role of PARP in diabetic vascular injury is now supported by noveltools, such as new classes of potent inhibitors of PAR-P and genetically engineered animals lacking the gene for PARR Pharmacological inhibition of PARP emerges as a potential approach for the experimental therapy of diabetic vascular dysfunction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 07:29:01