Modulation of the induction of rat hepatic cytochromes P-450 by selenium deficiency.
The induction by phenobarbital of liver microsomal cytochrome P-450 has been demonstrated to be impaired in rats fed a selenium-deficient diet. Cytochrome P-450 isozyme specific immunologic and molecular techniques were used in the present study to better define the role of selenium in the induction of cytochrome P-450 by phenobarbital. Phenobarbital treatment of the selenium-deficient rats resulted in an increase in the level of total cytochrome P-450 50% of that observed with control rats and in a 10-fold increase in microsomal heme oxygenase. Quantitative immunoblot analyses demonstrated that the levels of cytochromes P-450b + e and P-450p in the phenobarbital-treated selenium-deficient rats were approximately 50% of those found in the phenobarbital-treated control rats. Finally, RNA hybridization studies using cDNA probes to cytochromes P-450b + e or P-450p demonstrated that the accumulations of the RNAs encoding these cytochromes P-450 were unaffected by the selenium status of the rats. These studies suggest that the impaired phenobarbital induction of the cytochromes P-450 in the selenium-deficient rats is the result of an increase in the degradation of the cytochromes P-450 or a decrease in the translation of the mRNAs coding for them.
Wrighton
S A
SA
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Elswick
B
B
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D015336:Molecular Probe Techniques; D010634:Phenobarbital / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency*
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); D012643:Selenium; D010634:Phenobarbital