Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
VALIDATION OF 4-NITROPHENOL AS AN IN-VITRO SUBSTRATE PROBE FOR HUMAN LIVER CYP2E1 USING CDNA EXPRESSION AND MICROSOMAL KINETIC TECHNIQUES
Autore:
TASSANEEYAKUL W; VERONESE ME; BIRKETT DJ; GONZALEZ FJ; MINERS JO;
Indirizzi:
FLINDERS MED CTR,DEPT CLIN PHARMACOL,BEDFORD PK ADELAIDE SA 5042 AUSTRALIA FLINDERS MED CTR,DEPT CLIN PHARMACOL ADELAIDE SA 5042 AUSTRALIA NIH,MOLEC CARCINOGENESIS LAB BETHESDA MD 20892
Titolo Testata:
Biochemical pharmacology
fascicolo: 11, volume: 46, anno: 1993,
pagine: 1975 - 1981
SICI:
0006-2952(1993)46:11<1975:VO4AAI>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ETHANOL-INDUCIBLE CYTOCHROME-P-450; PARA-NITROPHENOL; RAT-LIVER; IMMUNOCHEMICAL EVIDENCE; REDUCTIVE METABOLISM; BENZENE METABOLISM; ISOZYME 3A; OXIDATION; INDUCTION; HYDROXYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
W. Tassaneeyakul et al., "VALIDATION OF 4-NITROPHENOL AS AN IN-VITRO SUBSTRATE PROBE FOR HUMAN LIVER CYP2E1 USING CDNA EXPRESSION AND MICROSOMAL KINETIC TECHNIQUES", Biochemical pharmacology, 46(11), 1993, pp. 1975-1981

Abstract

The involvement of human cytochrome P450 (CYP) 2E1 in the hydroxylation of 4-nitrophenol (4NP) to 4-nitrocatechol (4NC) has been investigated using cDNA expression and liver microsomal kinetic and inhibitor techniques. 4NP hydroxylation by human liver microsomes and cDNA-expressed human CYP2E1 exhibited Michaelis-Menten kinetics; the respective apparent K-m values were 30 +/- 7 and 21 mu M. Mutual competitive inhibition was observed for 4NP and chlorzoxazone (CZ) (an alternative humanCYP2E1 substrate) in liver microsomes, with close similarities between the calculated apparent K-m and K-i values for each individual compound. 4NP and CZ hydroxylase activities in microsomes from 18 liver donors varied to a similar extent (3.3- and 3.0-fold, respectively) and 4NP hydroxylase activity correlated significantly (r(s) greater than orequal to 0.75, P < 0.005) with both CZ hydroxylation and immunoreactive CYP2E1 content. The prototypic CYP2E1 inhibitor, diethyldithiocarbamate, was a potent inhibitor of 4NC formation and decreased 4NP hydroxylation by cDNA-expressed CYP2E1 and human liver microsomes in parallel. Probes for other human CYP isoforms namely (alpha-naphthoflavone, coumarin, sulphaphenazole, quinidine, troleandomycin and mephenytoin) caused <15% inhibition of liver microsomal 4NP hydroxylation. These data confirm that, as in animal species, 4NP hydroxylation is catalysed largely by CYP2E1 in human liver and 4NP may therefore be used as an invitro substrate probe for the human enzyme.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 23:17:18