Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics.
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Krusekopf S, Roots I, Hildebrandt AG, Kleeberg U
Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics.
Xenobiotica. 2003 Feb;33(2):107-18.
- PubMed ID
- 12623754 [ View in PubMed]
- Abstract
1. Xenobiotic-mediated regulation of mRNA expression of all members of the human cytochrome P450 (CYP) 1 family has been measured by RT-PCR in the hepatoma cell line, HepG2. Besides the positive control beta -naphthoflavone, the H(+)/K(+)-ATPase inhibitors omeprazole, lansoprazole, pantoprazole and rabeprazole and the anti-malaria drug primaquine were included in this study. 2. beta-Naphthoflavone, primaquine, omeprazole and lansoprazole increased mRNA levels of CYP1A1, CYP1A2 and CYP1B1. Induction by rabeprazole was significant only for CYP1A1 and CYP1A2, whereas none of the CYP1 mRNAs was induced by pantoprazole. This result was confirmed in primary human hepatocytes. 3. Transcriptional regulation was proved by inhibition of induction with actinomycin D. 4. Increase of CYP1 mRNA was significant after 1 h and maximal after 4 h. CYP1B1, but not CYP1A1 or CYP1A2, was dramatically down-regulated between 4 and 24 h. This decrease was prevented by treatment of cells with actinomycin D after induction, indicating an active transcription-dependent mechanism of CYP1B1 mRNA degradation. 5. In conclusion, xenobiotics inducing CYP1A1 mRNA expression have been shown also to induce CYP1A2 and CYP1B1, differing only with regard to level and time course of induction.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Lansoprazole Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Lansoprazole Cytochrome P450 1B1 Protein Humans UnknownInducerDetails Omeprazole Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Omeprazole Cytochrome P450 1B1 Protein Humans UnknownInducerDetails Primaquine Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Primaquine Cytochrome P450 1A2 Protein Humans UnknownSubstrateInducerDetails Primaquine Cytochrome P450 1B1 Protein Humans UnknownInducerDetails Rabeprazole Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Rabeprazole Cytochrome P450 1A2 Protein Humans UnknownInhibitorInducerDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome beta-Naphthoflavone Experimental CYP1A1 1543 upregulated beta-Naphthoflavone results in increased expression of CYP1A1 mRNA 15q24.1 beta-Naphthoflavone Experimental CYP1A2 1544 upregulated beta-Naphthoflavone results in increased expression of CYP1A2 mRNA 15q24.1 beta-Naphthoflavone Experimental CYP1B1 1545 upregulated beta-Naphthoflavone results in increased expression of CYP1B1 mRNA 2p22.2 Lansoprazole Approved Investigational CYP1A1 1543 upregulated Lansoprazole results in increased expression of CYP1A1 mRNA 15q24.1 Lansoprazole Approved Investigational CYP1A2 1544 upregulated Lansoprazole results in increased expression of CYP1A2 mRNA 15q24.1 Lansoprazole Approved Investigational CYP1B1 1545 upregulated Lansoprazole results in increased expression of CYP1B1 mRNA 2p22.2 Omeprazole Approved Investigational Vet Approved CYP1A1 1543 upregulated Omeprazole results in increased expression of CYP1A1 mRNA 15q24.1 Omeprazole Approved Investigational Vet Approved CYP1A2 1544 upregulated Omeprazole results in increased expression of CYP1A2 mRNA 15q24.1 Omeprazole Approved Investigational Vet Approved CYP1B1 1545 upregulated Omeprazole results in increased expression of CYP1B1 mRNA 2p22.2 Primaquine Approved CYP1A1 1543 upregulated Primaquine results in increased expression of CYP1A1 mRNA 15q24.1 Primaquine Approved CYP1A2 1544 upregulated Primaquine results in increased expression of CYP1A2 mRNA 15q24.1 Primaquine Approved CYP1B1 1545 upregulated Primaquine results in increased expression of CYP1B1 mRNA 2p22.2 Rabeprazole Approved Investigational CYP1A1 1543 upregulated Rabeprazole results in increased expression of CYP1A1 mRNA 15q24.1 Rabeprazole Approved Investigational CYP1A2 1544 upregulated Rabeprazole results in increased expression of CYP1A2 mRNA 15q24.1