MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Porter, T. D.
Right arrow Articles by Coon, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Porter, T. D.
Right arrow Articles by Coon, M. J.

Induction and tissue-specific expression of rabbit cytochrome P450IIE1 and IIE2 genes

TD Porter, SC Khani and MJ Coon

Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor 48109.

Treatment of rabbits with a variety of dissimilar chemicals, including ethanol, acetone, and imidazole, results in elevated levels of hepatic and renal cytochrome P-450 form 3a, also designated P-450ALC or P- 450IIE. The P450IIE1 subfamily in rabbits is composed of two genes that encode proteins with 97% sequence identity; the mRNAs from these genes can be distinguished by their differing electrophoretic mobilities. In the present studies, examination of the expression of these genes revealed that P450IIE1 (gene 1) mRNA is present in greatest abundance in the liver, is present in kidney and nasal mucosa at approximately 10% of the level in liver, and is present in lung at approximately 5% of the level in liver. P450IIE2 (gene 2) mRNA is present in liver and lung at approximately 50% of the level of gene 1 mRNA in these tissues but cannot be detected in kidney or nasal mucosa. Neither gene is expressed in testis, ovary, small intestine, or adrenal tissue. Treatment of rabbits with acetone or imidazole results in elevated levels of P-450 3a-immunoreactive protein in liver and kidney without concomitant increases in P450IIE gene mRNAs. Moreover, various lengths of ethanol treatment elevated the level of immunoreactive protein in liver and kidney, with a rapid reduction of gene 1 mRNA and, at 14 days, gene 2 mRNA to approximately 50% of control levels. In contrast to these chemical inducers of 3a, fasting for 48 hr significantly increases gene 1 and 2 mRNA in liver but does not increase the level of immunoreactive protein. These results indicate that the rabbit P450IIE genes are not coordinately expressed or regulated and, as found with the rat ortholog P-450j, chemical inducers of 3a evidently act through changes in the rate of synthesis or degradation of the enzyme, rather than through increased gene transcription.

Volume 36, Issue 1, pp. 61-65, 07/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
M. Joshi and R. F. Tyndale
INDUCTION AND RECOVERY TIME COURSE OF RAT BRAIN CYP2E1 AFTER NICOTINE TREATMENT
Drug Metab. Dispos., April 1, 2006; 34(4): 647 - 652.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. D. Porter
JUD COON: 35 YEARS OF P450 RESEARCH, A SYNOPSIS OF P450 HISTORY
Drug Metab. Dispos., January 1, 2004; 32(1): 1 - 6.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics