Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker rats: effect of phenobarbital treatment

Abhik M Bandyopadhyay; Inder  Chaudhary; Larry W Robertson; Brian Gemzik; Andrew Parkinson; Robert A Blouin

doi:10.1006/abbi.1993.1604

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Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker rats: effect of phenobarbital treatment

Journal article

Peer reviewed

Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker rats: effect of phenobarbital treatment

Abhik M Bandyopadhyay, Inder Chaudhary, Larry W Robertson, Brian Gemzik, Andrew Parkinson and Robert A Blouin

Archives of biochemistry and biophysics, Vol.307(2), pp.386-390

12/1993

DOI: 10.1006/abbi.1993.1604

PMID: 8274026

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Abstract

The present study determined the effect of genetic obesity and phenobarbital (PB) treatment on the expression and regulation of the hepatic cytochrome P450 enzyme (CYP2C11) in Fa/? and fa/fa Zucker rats. Hepatic CYP2C11 levels as determined by Western immunoblotting and associated enzymatic activity (testosterone oxidation at the 2 alpha position) were significantly lower in untreated fa/fa Zucker rats compared with that observed in Fa/? Zucker rats. There was no significant difference in the constitutive CYP2C11 steady-state mRNA level hybridizable to the cDNA (P450 16 alpha) or specific oligonucleotide probe (Northern and slot blot analyses) between fa/fa and Fa/? Zucker rats. The depressed constitutive CYP2C11 protein levels in fa/fa rats may be attributed to their low plasma testosterone and growth hormone levels; however, lack of differences in CYP2C11 steady-state mRNA suggest post-transcriptional regulatory mechanism(s). Treatment with PB further suppressed hepatic CYP2C11 protein levels and activities in both fa/fa and Fa/? Zucker rats in comparison with that seen in controls. The level of CYP2C11 steady-state mRNA was significantly higher after treatment with PB in Fa/? Zucker rats, while no change was observed in fa/fa animals. The mechanism by which PB treatment fails to increase CYP2C11 steady-state mRNA levels in the fa/fa Zucker rat is unknown; however, it may share a common molecular basis with the defect in nuclear transcription rate previously observed with CYP2B1/2B2.

DNA

Phenobarbital - pharmacology

Gene Expression Regulation, Enzymologic - drug effects

Body Weight - drug effects

Molecular Sequence Data

RNA, Messenger - analysis

Male

Steroid 16-alpha-Hydroxylase

Obesity - genetics

Cytochrome P450 Family 2

Testosterone - metabolism

Isoenzymes - metabolism

Microsomes, Liver - drug effects

Base Sequence

Steroid Hydroxylases - genetics

Isoenzymes - genetics

Rats

Sex Characteristics

Rats, Zucker

Homozygote

Organ Size - drug effects

Animals

Cytochrome P-450 Enzyme System - biosynthesis

Cytochrome P-450 Enzyme System - genetics

Heterozygote

Obesity - enzymology

Aryl Hydrocarbon Hydroxylases

Steroid Hydroxylases - biosynthesis

Details

Title: Subtitle: Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker rats: effect of phenobarbital treatment
Creators: Abhik M Bandyopadhyay - Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536
Inder Chaudhary
Larry W Robertson
Brian Gemzik
Andrew Parkinson
Robert A Blouin
Resource Type: Journal article
Publication Details: Archives of biochemistry and biophysics, Vol.307(2), pp.386-390
Publisher: United States
DOI: 10.1006/abbi.1993.1604
PMID: 8274026
ISSN: 0003-9861
eISSN: 1096-0384
Grant note: GM 42058 / NIGMS NIH HHS ES 03765 / NIEHS NIH HHS
Language: English
Date published: 12/1993
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002423902771

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12 Times Cited - Web of Science