TY - JOUR
T1 - Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa zucker rats
T2 - Effect of phenobarbital treatment
AU - Bandyopadhyay, Abhik M.
AU - Chaudhary, Inder
AU - Robertson, Larry W.
AU - Gemzik, Brian
AU - Parkinson, Andrew
AU - Blouin, Robert A.
PY - 1993
Y1 - 1993
N2 - The present study determined the effect of genetic obesity and phenobarbital (PB) treatment on the expression and regulation of the hepatic cytochrome P450 enzyme (CYP2CL1) in Fa/? and fa/fa Zucker rats. Hepatic CYP2C1 1 levels as determined by Western immunoblotting and associated enzymatic activity (testosterone oxidation at the 2α 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 16α) 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.
AB - The present study determined the effect of genetic obesity and phenobarbital (PB) treatment on the expression and regulation of the hepatic cytochrome P450 enzyme (CYP2CL1) in Fa/? and fa/fa Zucker rats. Hepatic CYP2C1 1 levels as determined by Western immunoblotting and associated enzymatic activity (testosterone oxidation at the 2α 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 16α) 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.
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U2 - 10.1006/abbi.1993.1604
DO - 10.1006/abbi.1993.1604
M3 - Article
C2 - 8274026
AN - SCOPUS:0027142917
SN - 0003-9861
VL - 307
SP - 386
EP - 390
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -