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Titolo:
STABLE EXPRESSION OF HUMAN CYTOCHROME-P450 3A4 IN CONJUNCTION WITH HUMAN NADPH-CYTOCHROME P450 OXIDOREDUCTASE IN V79 CHINESE-HAMSTER CELLS
Autore:
SCHNEIDER A; SCHMALIX WA; SIRUGURI V; DEGROENE EM; HORBACH GJ; KLEINGEIST B; LANG D; BOCKER R; BELLOC C; BEAUNE P; GREIM H; DOEHMER J;
Indirizzi:
TECH UNIV MUNICH,INST TOXIKOL & UMWELTHYG,LAZARETTSTR 62 D-80636 MUNCHEBERG GERMANY TECH UNIV MUNICH,INST TOXIKOL & UMWELTHYG D-80636 MUNCHEBERG GERMANY INDIAN COUNCIL MED RES,NATL INST NUTR HYDERABAD 500007 ANDHRA PRADESHINDIA UNIV UTRECHT,TOXICOL RES INST NL-3508 TD UTRECHT NETHERLANDS UNIV ERLANGEN NURNBERG,INST EXPT & KLIN PHARMAKOL & TOXIKOL NURNBERG GERMANY CHU NECKAR PARIS FRANCE GSF FORSCHUNGSZENTRUM,INST TOXIKOL OBERSCHLEISSHEIM GERMANY
Titolo Testata:
Archives of biochemistry and biophysics
fascicolo: 2, volume: 332, anno: 1996,
pagine: 295 - 304
SICI:
0003-9861(1996)332:2<295:SEOHC3>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER; METABOLIC-ACTIVATION; NIFEDIPINE OXIDASE; CATALYTIC ACTIVITIES; ESCHERICHIA-COLI; CDNA; OXIDATION; ENZYME; YEAST; MUTAGENICITY;
Keywords:
CYTOCHROME P450 3A4; NADPH-CYTOCHROME P450 REDUCTASE; METABOLISM; TESTOSTERONE; NIFEDIPINE; MIDAZOLAM; V79 CHINESE HAMSTER CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
A. Schneider et al., "STABLE EXPRESSION OF HUMAN CYTOCHROME-P450 3A4 IN CONJUNCTION WITH HUMAN NADPH-CYTOCHROME P450 OXIDOREDUCTASE IN V79 CHINESE-HAMSTER CELLS", Archives of biochemistry and biophysics, 332(2), 1996, pp. 295-304

Abstract

V79 Chinese hamster cells were constructed for stable expression of human cytochrome P450 3A4 with and without coexpression of human NADPH-cytochrome P450 oxidoreductase. Expression of the cDNAs was shown by Northern and Western analyses. Activity was tested by 6 beta-hydroxylation of testosterone for cytochrome P450 3A4 and by cytochrome c reduction for NADPH-cytochrome P450 reductase. Five V79 cell lines were obtained expressing cytochrome P450 3A4, human NADPH-cytochrome P450 oxidoreductase, and both. Cytochrome P450 3A4 activity depended highly on cytochrome P450 reductase activity, with lowest activity when only the parental Chinese hamster cytochrome P450 reductase was present, 5- and10-fold higher when coexpressed with the human NADPH-cytochrome P450 reductase. Correspondingly, cytotoxic and genotoxic potency of aflatoxin B1 was increased by orders of magnitudes when human cytochrome P4503A4 was coexpressed with the human NADPH-cytochrome P450 reductase. The effect of NADPH-cytochrome P450 reductase coexpression on cytochrome P450 3A4 activity was also tested by nifedipine oxidation and midazolam hydroxylation. Nifedipine oxidation was increased about 10-fold, 1-hydroxylation of midazolam and 4-hydroxylation of midazolam were increased 15-fold. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 22:02:08