| Autor: |
D K Strom, Usha R. Pendurthi, Robert H. Tukey, C L Potenza, Keith J. Griffin, Eric F. Johnson, George E. Schwab |
| Rok vydání: |
1989 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 264:16222-16228 |
| ISSN: |
0021-9258 |
| DOI: |
10.1016/s0021-9258(18)71610-4 |
| Popis: |
The macrolide antibiotic rifampicin is a potent inducer of cytochrome P-450-mediated drug metabolism in humans and rabbits. In this report, we demonstrate that in immature rabbits, rifampicin activates the transcription of the Cyp3A6 gene which encodes P450IIIA6 (cytochrome P-450 3c). The maximum increase in transcription was seen at 12 h following administration of rifampicin. Northern and slot blot analyses indicate that mRNAs corresponding to P450IIIA6 accumulates during the period of increased transcription and persist at 18 h when the rate of transcription has returned to basal levels. P450IIIA6 protein accumulates in liver microsomes over this period. At 24 h a greater than 10-fold increase in microsomal P450IIIA6 protein is detected by immunoblotting using a monoclonal antibody to P450IIIA6. The rate of microsomal progesterone 6 beta-hydroxylase activity is also elevated when compared to untreated rabbits, and this enzyme is activated in vitro by alpha-naphthoflavone. To determine whether this enzyme is stimulated by alpha-naphthoflavone in intact cells, COS-1 cells were transfected with an expression vector harboring the coding region of a P450IIIA6 cDNA. Our results demonstrate that the transfected COS-1 cells exhibit progesterone 6 beta-hydroxylase activity that is stimulated by alpha-naphthoflavone added to the culture medium. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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