INDUCTION OF CYP2E1 IN LIVER, KIDNEY, BRAIN AND INTESTINE DURING CHRONIC ETHANOL ADMINISTRATION AND WITHDRAWAL - EVIDENCE THAT CYP2E1 POSSESSES A RAPID PHASE HALFLIFE OF 6 HOURS OR LESS

被引:97
作者
ROBERTS, BJ [1 ]
SHOAF, SE [1 ]
JEONG, KS [1 ]
SONG, BJ [1 ]
机构
[1] NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20892
关键词
D O I
10.1006/bbrc.1994.2774
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Controversy exists as to whether the induction of CYP2E1 by ethanol occurs via increased protein synthesis or protein stabilization. To address these issues in vivo, we chronically administered ethanol to rats and determined levels of immunoreactive CYP2E1 in liver, kidney, brain and upper gastro-intestinal tract (GI). Our data shows that chronic ethanol administration induces hepatic (5-6-foId over pair-fed controls) and extra-hepatic CYP2E1, an effect which is strikingly absent 12 hours after ethanol withdrawal. No changes in CYP2E1 mRNA were observed at any time, suggesting these changes are mainly post-translational at a blood ethanol concentration of 0.15% w/v. Our experimental data indicates that CYP2E1 possesses a half-life of 6 hours or less in the liver and is rapidly degraded following the removal of ethanol. This pattern of CYP2E1 turnover was also observed in other tissues, suggestive of a similar mode of regulation. (C) 1994 Academic Press, Inc.
引用
收藏
页码:1064 / 1071
页数:8
相关论文
共 21 条
[1]   CYTOCHROME-P-450 ISOZYME PATTERN IS RELATED TO INDIVIDUAL SUSCEPTIBILITY TO DIETHYLNITROSAMINE-INDUCED LIVER-CANCER IN RATS [J].
AITIO, A ;
AITIO, ML ;
CAMUS, AM ;
CARDIS, E ;
BARTSCH, H .
JAPANESE JOURNAL OF CANCER RESEARCH, 1991, 82 (02) :146-156
[2]   INDUCTION OF CYTOCHROME-P450 2E1 DURING CHRONIC ETHANOL EXPOSURE OCCURS VIA TRANSCRIPTION OF THE CYP 2E1 GENE WHEN BLOOD-ALCOHOL CONCENTRATIONS ARE HIGH [J].
BADGER, TM ;
HUANG, J ;
RONIS, M ;
LUMPKIN, CK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 190 (03) :780-785
[3]   MECHANISM OF INDUCTION OF CYTOCHROME-P-450AC(P-450J) IN CHEMICALLY-INDUCED AND SPONTANEOUSLY DIABETIC RATS [J].
DONG, ZG ;
HONG, JY ;
MA, Q ;
LI, DC ;
BULLOCK, J ;
GONZALEZ, FJ ;
PARK, SS ;
GELBOIN, HV ;
YANG, CS .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1988, 263 (01) :29-35
[4]   SUBSTRATE-REGULATED, HORMONE-REGULATED, AND CAMP-REGULATED CYTOCHROME P450 DEGRADATION [J].
ELIASSON, E ;
JOHANSSON, I ;
INGELMANSUNDBERG, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (08) :3225-3229
[5]   LIGAND-DEPENDENT MAINTENANCE OF ETHANOL-INDUCIBLE CYTOCHROME-P-450 IN PRIMARY RAT HEPATOCYTE CELL-CULTURES [J].
ELIASSON, E ;
JOHANSSON, I ;
INGELMANSUNDBERG, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 150 (01) :436-443
[6]  
ELIASSON E, 1992, J BIOL CHEM, V267, P15765
[7]   THE INDUCTION OF A SPECIFIC FORM OF CYTOCHROME-P-450 (P-450J) BY FASTING [J].
HONG, JY ;
PAN, JM ;
GONZALEZ, FJ ;
GELBOIN, HV ;
YANG, CS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 142 (03) :1077-1083
[8]  
INGELMANSUNDBER.M, 1993, ALCOHOL, V10, P447
[10]   TRANSLATIONAL ACTIVATION OF ETHANOL-INDUCIBLE CYTOCHROME-P450 (CYP2E1) BY ISONIAZID [J].
PARK, KS ;
SOHN, DH ;
VEECH, RL ;
SONG, BJ .
EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION, 1993, 248 (01) :7-14