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Titolo:
INHIBITION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE BY EBSELEN - PREVENTION BY THIOLS SUGGESTS THE INACTIVATION BY EBSELEN OF A CRITICAL THIOL ESSENTIAL FOR THE CATALYTIC ACTIVITY OF NITRIC-OXIDE SYNTHASE
Autore:
ZEMBOWICZ A; HATCHETT RJ; RADZISZEWSKI W; GRYGLEWSKI RJ;
Indirizzi:
UNIV TEXAS,SCH MED,DIV HEMATOL,6431 FANNIN HOUSTON TX 77030 NICHOLAS COPERNICUS MED ACAD,DEPT PHARMACOL PL-31531 KRAKOW POLAND
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 267, anno: 1993,
pagine: 1112 - 1118
SICI:
0022-3565(1993)267:3<1112:IOENSB>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PEROXIDASE-LIKE ACTIVITY; RELAXING FACTOR; L-ARGININE; MOLECULAR-CLONING; ORGANOSELENIUM COMPOUND; MACROPHAGE OXIDATION; ISOLATED HEPATOCYTES; MURINE MACROPHAGES; LIPID-PEROXIDATION; PZ-51 EBSELEN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
A. Zembowicz et al., "INHIBITION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE BY EBSELEN - PREVENTION BY THIOLS SUGGESTS THE INACTIVATION BY EBSELEN OF A CRITICAL THIOL ESSENTIAL FOR THE CATALYTIC ACTIVITY OF NITRIC-OXIDE SYNTHASE", The Journal of pharmacology and experimental therapeutics, 267(3), 1993, pp. 1112-1118

Abstract

NO synthase (NOS) is a unique P-450-type enzyme containing both a reductase and a heme domain on a single polypeptide. We show that ebselen[Ebs, 2-phenyl-1,2-benzisoselenazol-3-(2H) one], a nontoxic selenoorganic compound known to break a cysteine thiolate/Fe... bond of some ofP-450 enzymes, is a relatively selective inhibitor of endothelial isoform of NOS. In rings of rabbit aorta, Ebs irreversibly blocked both the basal as well as acetylcholine- or calcium ionophore A23187-stimulated release of nitric oxide with an IC50 of 6 muM. In homogenates of bovine aortic endothelial cells, Ebs inhibited the activity of NOS, assayed by monitoring conversion of L-[2,3-H-3]arginine to L-[2,3-H-3]citrulline, with an IC50 of 8.5 muM. The inhibitory action of Ebs tol (30-500 muM). The prevention by thiols of Ebs-induced inhibition of NOS suggests that these are competing with a thiol group of NOS that is essential for the catalytic activity of the enzyme. The consequence of the presence of thiols is the 'trapping'' of Ebs in the form of inactiveselenyl sulfides. Consistent with the proposed mechanism of action ofEbs is lack of activity of diselenide of Ebs, which also demonstratesthat the action of Ebs is independent of its glutathione peroxidase-like activity. In comparison to endothelial preparations, IC50 values of Ebs for inhibition of soluble isoforms of NOS present in homogenatesof porcine cerebellum and of spleens obtained from lipopolysaccharide-treated rats were more than 30-fold higher.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 01:55:41