Mechanism of induction of cytochrome P-450 by phenobarbital

M. Adesnik, S. Bar-Nun, F. Maschio, M. Zunich, A. Lippman, E. Bard

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment of rats with phenobarbital (PB) leads to a substantial increase in the hepatic levels of translatable polysomal poly(A) + cytochrome P-450 mRNA. An enriched fraction of P-450 mRNA was obtained by agarose gel electrophoresis and used to prepare a cDNA probe by differential hybridization to total mRNA from control and PB-treated rats. The majority of the sequences within the probe hybridized to recombinant DNA plasmids which contained a bona fide P-450 cDNA insert identified by positive hybridization selection and in vitro translation. The cDNA probe was used to demonstrate that PB treatment leads to a 30-fold increase in polysomal P-450 mRNA, which is not due to more efficient utilization of previously existing mRNA but to the appearance of new messenger in the cytoplasm. The induction of cytoplasmic P-450 mRNA by PB was rapid, with increases detected within 3 h of PB injection and steady state levels reached in approximately 20h. The data suggest that the increase in cytoplasmic P-450 protein levels observed after PB treatment may be totally accounted for by an enhanced rate of synthesis resulting from translation of higher cytoplasmic levels of its specific mRNA. The P-450 mRNA was almost exclusively segregated into the membrane-bound polysome compartment as expected for an mRNA coding for an integral membrane of protein of endoplasmic reticulum.

Original languageEnglish
Pages (from-to)10340-10345
Number of pages6
JournalJournal of Biological Chemistry
Volume256
Issue number20
StatePublished - 1981
Externally publishedYes

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