Differential induction and tissue-specific expression of closely related members of the phenobarbital-inducible rabbit cytochrome P-450 gene family

• Published in: The Journal of biological chemistry Vol. 259; no. 18; pp. 11165 - 11168
• Main Authors: Leighton, J K, Kemper, B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25-09-1984; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Biological and medical sciences; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - genetics; DNA - analysis; Enzyme Induction; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Isoenzymes - biosynthesis; Kidney - enzymology; Liver - enzymology; Lung - enzymology; Male; Molecular and cellular biology; Molecular genetics; Nucleic Acid Hybridization; Phenobarbital - pharmacology; Rabbits; RNA - analysis; Time Factors; Tissue Distribution; Vertebrata; Hemoprotein; Mammalia; Messenger RNA; Gene; Induction; Cytochrome P450; Liver; Rabbit; Lagomorpha; Gene expression; Kidney
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)90839-2

We have examined the tissue-specific expression of three rabbit genes that are closely related members of a subfamily of the phenobarbital-inducible cytochrome P-450 gene family. Analysis of the levels of mRNA in liver revealed that (a) cytochrome P-450PBc1 mRNA was not detectable in livers from control animals but was present in livers from animals treated with phenobarbital, (b) cytochrome P-450PBc2 was present in control tissue and was increased by about 3-fold 24 h after phenobarbital treatment, and (c) the levels of cytochrome P-450PBc3 mRNA was the same in livers from control and treated animals. In the kidney, only P-450PBc2 mRNA was detected at a level 15% of that in the liver, and the levels increased about 3-fold after phenobarbital treatment. None of the mRNAs was detected in lung tissue. Multiple species of RNA were observed that hybridized to probes for cytochrome P-450PBc1 and P-450PBc2 cDNAs by Northern blot analysis ranging in size from 2300 to 4000 nucleotides. Differential sites for polyadenylation probably cause the heterogeneity in size. A single species of RNA of 2200 nucleotides that hybridized to cytochrome P-450PBc3 cDNA probes was observed. These data demonstrate that three closely related cytochrome P-450 genes are differentially responsive to phenobarbital treatment and that they exhibit different tissue-specific patterns of expression.