PMID: 2870681Apr 1, 1986Paper

Regulation of cytochrome P-450c by glucocorticoids and polycyclic aromatic hydrocarbons in cultured fetal rat hepatocytes

Archives of Biochemistry and Biophysics
J M MathisE R Simpson

Abstract

The actions of polycyclic aromatic hydrocarbons and glucocorticoids to regulate the synthesis of cytochrome P-450c (the major isozyme induced by polycyclic aromatic hydrocarbons) were investigated in fetal rat hepatocytes maintained in primary monolayer culture. Treatment of hepatocytes in culture with 1,2-benzanthracene resulted in a 50-fold increase in 7-ethoxycoumarin O-deethylase activity. The level of P-450c increased in the cells in a time-dependent fashion as determined by immunoelectrophoretic analysis. The inductive effect of BA was potentiated approximately 1.6- to 2.3-fold when 1 microM dexamethasone was included in the culture medium. However, dexamethasone alone had little or no effect on the induction of P-450c. The rate of synthesis of P-450c was examined by immunoisolation of the specific isozyme from total cellular proteins radiolabeled with [35S]methionine and from the protein products formed during in vitro translation of the isolated mRNA. In addition, the amount of mRNA specific for cytochrome P-450c was determined by Northern blot analysis of RNA extracted from cultured cells. The changes in the rates of synthesis and mRNA levels were found to parallel the changes in enzyme activity. The concentration of d...Continue Reading

References

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Citations

Jan 1, 1990·Pharmacology & Therapeutics·A B Okey
Dec 1, 1988·Molecular and Cellular Endocrinology·J M MathisR A Prough
Mar 1, 1993·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·P C LeeJ J Lech
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Apr 6, 2000·The Biochemical Journal·P Honkakoski, M Negishi
Aug 1, 1993·In Vitro Cellular & Developmental Biology. Animal·A K Dasmahapatra, P C Lee
May 21, 2010·Drug Metabolism Reviews·Zdenek Dvorak, Peotr Pavek
Jul 25, 2009·Drug Metabolism Reviews·Katalin MonostoryZdenek Dvorak
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Nov 26, 1986·Biochemical and Biophysical Research Communications·K T ShiverickM O James

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