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Titolo:
INHIBITION OF ERYTHROCYTE SELENIUM-GLUTATHIONE PEROXIDASE BY AURANOFIN ANALOGS AND METABOLITES
Autore:
ROBERTS JR; SHAW CF;
Indirizzi:
UNIV WISCONSIN,DEPT CHEM,POB 413 MILWAUKEE WI 53201 UNIV WISCONSIN,DEPT CHEM MILWAUKEE WI 53201
Titolo Testata:
Biochemical pharmacology
fascicolo: 8, volume: 55, anno: 1998,
pagine: 1291 - 1299
SICI:
0006-2952(1998)55:8<1291:IOESPB>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIGAND-EXCHANGE REACTIONS; GOLD COMPOUNDS; BLOOD-CELLS; MECHANISM; EFFLUX;
Keywords:
AURANOFIN; GOLD(I) THIOGLUCOSE; BIS(GLUTATHIONATO)GOLD(I); INHIBITION CONSTANTS; SELENIUM-GLUTATHIONE PEROXIDASE; ERYTHROCYTES; SERUM ALBUMIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
J.R. Roberts e C.F. Shaw, "INHIBITION OF ERYTHROCYTE SELENIUM-GLUTATHIONE PEROXIDASE BY AURANOFIN ANALOGS AND METABOLITES", Biochemical pharmacology, 55(8), 1998, pp. 1291-1299

Abstract

The effect of oold ligation on the inhibition of bovine erythrocyte selenium-glutathione peroxidase (GSH-Px) was examined. The anti-arthritic drug auranofin ,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S) (triethylphosphine) gold(I)] (Et(3)PAuSATg) and its analogue, Et3PAuCl,exhibited experimentally equivalent K-i values (11.6 +/- 0.8 and 10.8+/- 0.5 mu M, respectively), despite the greatly disparate affinitiesof their ligands for gold(I): ,4,6-tetr-O-acetyl-1-thiolato-beta-D-glucopyranose (ATgS(-)) >> Cl-. This similarity reflects ligand exchangereactions that generate the glutathione complex Et(3)PAuSG from the excess glutathione (GSH, 1 mM) used in the assay. The K-i values for bis(glutathionato)gold(I) (Au(SG)(2)(-)) and gold(I) thioglucose (AuSTg)were also found to be equal (2.8 +/- 0.4 and 2.4 +/- 0.5 mu M, respectively). This confirms the previous postulate of Chaudiere and Tappel (J Inorg Biochem 20:313-325, 1984) that Au(SG)(2)(-) is generated fromAuSTg in the presence of excess glutathione. Since auranofin metabolites accumulate in red blood cells, the inhibition of intracellular GSH-Px was examined by using intact erythrocytes. There was greater inhibition of the reaction when the cells mere resuspended in isotonic buffer than in whole blood, because serum albumin in the latter competes for the auranofin and decreases the uptake by erythrocytes. After correction for the extent of gold uptake, the K-i values were determined tobe the same as those observed for Au(SG)(2)(-) in the extracellular assay, indicating loss of both the Et3P and ATgS(-) ligands from auranofin. Thus, the inhibition of GSH-Px by gold complexes is dependent on their ligation, and the ultimate gold(I) compound that interacts with erythrocyte GSH Px in intact red cells, Au(SG)(2)(-) is radically different from the original auranofin molecule. (C) 1998 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 05:10:20