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Expression of cytochromes P-450c and P-4 ... the post-transcriptional level
Expression of cytochromes P-450c and P-450d mRNAs in cultured rat hepatocytes. 3-Methylcholanthrene induction is regulated primarily at the post-transcriptional level.
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Primary cultures of adult rat hepatocytes grown in serum-free hormonally defined medium were shown, for the first time, to be capable of supporting the 3-methylcholanthrene-inducible expression of cytochrome P-450d. Such cultures were used to investigate the mechanism of the induction of cytochrome P-450c and P-450d mRNAs. After 1 day of growth in culture, P-450c and P-450d mRNAs were induced 33- and 28-fold, respectively, by 3-methylcholanthrene treatment. A similar magnitude of induction was achieved after 2-5 days growth in culture. However, the relative abundance of the two mRNAs before and after treatment decreased linearly over the 5-day time course. Kinetic analysis revealed that induction of both genes was rapid and could be observed less than 2 h following treatment. Accumulation of both mRNAs was linear for 8 h, reaching a plateau by 12 h. Expression then remained constant for at least 12 additional hours. In vitro nuclear run-on experiments revealed a 3.9- and 2.0-fold transcriptional induction of the P-450c and P-450d genes, respectively. This is in contrast to the large induction of accumulation of these mRNAs observed at steady state. Thus, the 3-methylcholanthrene induction of P-450c and P-450d mRNAs in the hepatocyte cultures appeared to be mediated primarily at the post-transcriptional level. Experiments on rat liver showed that, in vivo, P-450d is also regulated primarily at the post-transcriptional level. However, P-450c was found to be regulated primarily transcriptionally.
Silver G, Krauter KS
The Journal of biological chemistry
1988-08-25 00:00
263
24
11802-7
Animals,Cell Nucleus,Cells, Cultured,Cytochrome P-450 Enzyme System,Gene Expression Regulation,Kinetics,Liver,Methylcholanthrene,Nucleic Acid Hybridization,RNA, Messenger,Rats,Rats, Inbred Strains,Transcription, Genetic,Uridine Triphosphate,RNA, Messenger,Methylcholanthrene,Uridine Triphosphate,Cytochrome P-450 Enzyme System
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461
J. Biol. Chem.
NCI CA31855, NCI CA39553, NIEHS ES05405
0021-9258
652
True
3403555
