Transcriptional Activation of Cytochrome P450 2B1/2 Genes in Rat Liver by Diallyl Sulfide, a Compound Derived from Garlic
| Autor: | Bing-Li Ma, Shu M. Ning, Jinmei M. Pan, C. S. Yang, Shanthi R. Paranawithana, Jun-Yan Hong |
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| Rok vydání: | 1993 |
| Předmět: |
Male
medicine.medical_specialty Transcription Genetic Molecular Sequence Data Biophysics RNA polymerase II Sulfides Biology Biochemistry Rats Sprague-Dawley Cytochrome P-450 Enzyme System Transcription (biology) Internal medicine medicine Animals Tissue Distribution RNA Messenger Molecular Biology Messenger RNA Base Sequence Cytochrome P450 Blotting Northern Rats Allyl Compounds medicine.anatomical_structure Endocrinology Liver Mechanism of action Enzyme Induction Cytochrome P-450 CYP2B1 Inactivation Metabolic Microsomes Liver Duodenum biology.protein Microsome medicine.symptom Oligonucleotide Probes Oxidoreductases Drug metabolism |
| Zdroj: | Archives of Biochemistry and Biophysics. 302:337-342 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.1993.1220 |
| Popis: | Previous work in our laboratory demonstrated that cytochrome P450 2B1 in rat liver was induced, but P450 2E1 was inhibited and inactivated, by diallyl sulfide (DAS), a compound derived from garlic. Such a selective effect on P450 enzymes is of considerable interest toward the understanding of dietary effects on xenobiotic metabolism. In the present study, the mechanism of P450 2B1 induction by DAS was investigated. Following a single dose of DAS (200 mg/kg body weight, ig), liver microsomal pentoxyresorufin dealkylase (PORd) activity, a representative activity of P450 2B1, was induced 3-, 16-, 26-, and 43-fold at 6, 12, 18, and 24 h after the treatment, respectively. A corresponding increase in the level of P450 2B 1/2 protein was observed by immunoblot analysis. The level of P450 2B1/2 mRNA in rat liver also increased markedly, reaching a maximum at 12 h after the DAS treatment. Hybridization with the isozyme-specific oligonucleotide probes revealed that the mRNA levels of both P450s 2B1 and 2B2 were induced. In contrast, the level of P450 2E1 mRNA in the liver of DAS-treated rats was not changed. The results of nuclear run-on assay revealed that the transcriptional rate of P450 2B1/2 genes in the rat liver increased 13-fold at 6 h after DAS administration and returned to the control value at 24 h. The transcription of P450 2B1/2 genes was blocked completely by α-amanitin, an inhibitor of RNA polymerase II. These results clearly demonstrate that the induction of P450 2B1/2 in rat liver by DAS is mainly due to transcriptional activation. In the DAS-treated rats, P450 2B1/2 mRNA was also markedly induced in the stomach and duodenum. The maximal induction was found at 12 h after the treatment while the levels of P450 2B1/2 mRNA increased 66-fold in the duodenum and 23-fold in the stomach. DAS treatment, however, did not change the levels of P450 2B1/2 mRNA in the lung and nasal mucosa. |
| Databáze: | OpenAIRE |
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