IMMUNOCHEMICAL DETECTION OF HUMAN LIVER CYTOCHROME-P450 FORMS RELATED TO PHENOBARBITAL-INDUCIBLE FORMS IN THE MOUSE

被引：31

作者：

RAUNIO, H

VALTONEN, J

HONKAKOSKI, P

LANG, MA

STAHLBERG, M

KAIRALUOMA, MA

RAUTIO, A

PASANEN, M

PELKONEN, O

机构：

[1] UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND

[2] UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND

[3] OULU UNIV,CENT HOSP,DEPT SURG,SF-90220 OULU,FINLAND

来源：

BIOCHEMICAL PHARMACOLOGY | 1990年 / 40卷 / 11期

基金：

芬兰科学院; 英国医学研究理事会;

关键词：

D O I：

10.1016/0006-2952(90)90092-Y

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Polyclonal antibodies generated to four distinct mouse liver phenobarbital-inducible cytochrome P450 isoforms were used to analyse related forms in human liver. N-terminal sequence analysis and biochemical properties of the P450s used as antigens suggest that they belong to P450 subfamilies IIB (P450PBI), IA (P450PBII), IIC (P450PBIII) and IIA (P450Coh). In immunoblot analysis, anti-P450PBII detected a single protein presumed to be P45 0IA2 in all the human livers tested. No proteins corresponding with P450IA1 could be detected. Anti-PBIII and anti-P450Coh antibodies each detected one band (54 and 48 kDa, respectively) in the liver samples. No bands were revealed by anti-P450PBI antibody. Protein dot-immunobinding analysis showed that P450s immunodetectable by anti-P450PBII, anti-P450PBIII and anti-P450Coh antibodies are expressed in human liver (range 9 to 69 pmol P450/mg protein). In immunoinhibition experiments the activity of 7-ethoxyresorufin O-deethylase (EROD) was blocked up to 90% by the anti-P450PBII antibody. Aryl hydrocarbon hydroxylase (AHH) was inhibited only by anti-P450PBIII, and coumarin 7-hydroxylase (COH) only by anti-P450Coh antibody. Testosterone hydroxylations in positions 6β, 7α, 15α and 16α were not affected significantly by any of the antibodies. These data suggest that the human liver P450IA2 is responsible for most of the elevated EROD activity, P450s in the IIC subfamily for constitutive AHH and P450s in the IIA subfamily for all of COH activity. © 1990.

引用

页码：2503 / 2509

页数：7

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