PMID: 6408085Jul 10, 1983Paper

Transcriptional regulation of rat liver epoxide hydratase, NADPH-Cytochrome P-450 oxidoreductase, and cytochrome P-450b genes by phenobarbital.

The Journal of Biological Chemistry
J P HardwickC B Kasper

Abstract

The relative rates of transcription of epoxide hydratase, NADPH-cytochrome P-450 oxidoreductase, and cytochrome P-450b genes were determined in purified hepatocyte nuclei isolated at different times after phenobarbital administration. The rates of transcription of the epoxide hydratase and oxidoreductase genes were increased 4- and 9-fold, respectively, above control levels 1 h after administration of the drug. Transcription rates for the oxidoreductase gene slowly decreased to control values at 24 h while transcription of the epoxide hydratase gene rapidly declined to approximately 2-fold above control values at 2.5 h and remained at this level up to 24 h after administration. Interestingly, transcription of the cytochrome P-450b gene followed a markedly different induction time course than the epoxide hydratase and oxidoreductase genes. Specifically, cytochrome P-450b gene transcription increased 23-fold above control values 6 to 8 h after phenobarbital administration and then slowly declined to 14-fold at 24 h. The increased levels of intranuclear pre-mRNA and cytoplasmic mRNA for each enzyme correlated well with transcriptional activity. In contrast to these results, the rate of transcription of the serum albumin gene was n...Continue Reading

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