Induction of 5-aminolevulinate synthase by drugs is independent of increased apocytochrome P450 synthesis

被引:29
作者
Jover, R [1 ]
Hoffmann, K [1 ]
Meyer, UA [1 ]
机构
[1] UNIV BASEL, BIOZENTRUM, CH-4052 BASEL, SWITZERLAND
关键词
D O I
10.1006/bbrc.1996.1325
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
To investigate the role of newly synthesized apocytochrome P450 (P450) in the regulation of 5-aminolevulinate synthase (ALAS), we overexpressed P450 in primary cultures of chick embryo hepatocytes and measured the subsequent effects on ALAS mRNA by semiquantitative RT-PCR. Hepatocytes were co-transfected with a vector for expression of P450 cDNAs (CYP3A4 or CYP2H1) and a vector directing the synthesis of a cell surface antibody. Transfected hepatocytes were isolated with hapten-coated magnetic beads at different times after electroporation (4, 8 and 20 h). Overexpression of human CYP3A4 was demonstrated by high levels of the corresponding mRNA and apoprotein as analyzed by RT-PCR and western-blot analysis. Similarly, chicken CYP2H1 was expressed to levels even higher than those induced with phenobarbital. However the level of ALAS mRNA did not change in these cells. Our results demonstrate that the induction of ALAS by drugs is not a direct consequence of increased P450 apoprotein synthesis and heme utilization. (C) 1996 Academic Press, Inc.
引用
收藏
页码:152 / 157
页数:6
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