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Titolo:
Cytochrome b(5) plays a key role in human microsomal chromium(VI) reduction
Autore:
Jannetto, PJ; Antholine, WE; Myers, CR;
Indirizzi:
Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA Med Coll Wisconsin Milwaukee WI USA 53226 oxicol, Milwaukee, WI 53226 USA Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA Med Coll Wisconsin Milwaukee WI USA 53226 s Inst, Milwaukee, WI 53226 USA
Titolo Testata:
TOXICOLOGY
fascicolo: 3, volume: 159, anno: 2001,
pagine: 119 - 133
SICI:
0300-483X(20010228)159:3<119:CBPAKR>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HEPATIC MICROSOMES; ONE-ELECTRON REDUCTION; CARCINOGEN CHROMATE; HEXAVALENT CHROMIUM; LIPID-PEROXIDATION; ENZYMATIC REDUCTION; HYDROGEN-PEROXIDE; FERRIC COMPLEXES; P-450 REDUCTASE; NUCLEIC-ACIDS;
Keywords:
chromium; cytochrome b(5); P450 reductase; proteoliposomes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Myers, CR Med Coll Wisconsin, Dept Pharmacol & Toxicol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA Med Coll Wisconsin 8701 Watertown Plank Rd Milwaukee WI USA 53226
Citazione:
P.J. Jannetto et al., "Cytochrome b(5) plays a key role in human microsomal chromium(VI) reduction", TOXICOLOGY, 159(3), 2001, pp. 119-133

Abstract

The reduction of chromium(VI) to Cr(III) results in the formation of reactive intermediates that contribute to the cytotoxicity, genotoxicity, and carcinogenicity of Cr(VI)-containing compounds. Previous studies suggest thathuman microsomal Cr(VI) reduction likely proceeds through cytochrome b(5). In order to better understand Cr(VI) toxicity in humans, the role of cytochrome b(5) in combination with P450 reductase was examined in the reductivetransformation of Cr(VI). Proteoliposomes containing human recombinant cytochrome b(5) and P450 reductase were constructed. The ability of P450 reductase to mediate efficient electron transfer from NADPH to cytochrome b(5) was confirmed by spectral analysis. The NADPH-dependent Cr(VI) reduction rate mediated by proteoliposomes was then compared to that of human microsomes. When these rates were normalized to equivalent cytochrome b(5) concentrations, the NADPH-dependent Cr(VI) reduction rates mediated by human microsomes were essentially identical to those for proteoliposomes containing cytochrome b(5) plus P450 reductase. Proteoliposomes containing only P450 reductase or cytochrome b(5) exhibited poor Cr(VI) reducing capabilities. Since it had been previously shown that trace amounts of iron (Fe) could dramatically stimulate microsomal Cr(VI) reduction, the ability of Fr to stimulate Cr(VI) reduction by proteoliposomes was examined. Both ferric chloride (FeCl3) and ferric adenosine-5'-diphosphate (FeADP) were shown to stimulate Cr(VI) reduction: this stimulation could be abolished by the addition of deferoxamine, a specific Fe(III) chelator. The NADPH-dependent reduction rates ofvarious ferric complexes by proteoliposomes were sufficient to account forthe increased Cr(VI) reduction rates seen with the addition of FeCl3 or FeADP. Cr(V) was detected by electron paramagnetic resonance (EPR) spectroscopy as a transient intermediate formed during NADPH-dependent Cr(VI) reduction mediated by proteoliposomes containing cytochrome b(5) and P450 reductase. Overall, cytochrome bi in combination with P450 reductase can account for the majority of the NADPH-dependent Cr(VI) reduction seen with human microsomes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/08/20 alle ore 08:06:48