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CYP Genes (cyp + gene)
Selected AbstractsCytochrome P450 gene expression levels in peripheral blood mononuclear cells in comparison with the liverCANCER SCIENCE, Issue 6 2004Motonobu Furukawa Cytochromes P450 (CYPs) compose a superfamily of similar proteins involved in detoxification and elimination, as well as activation of a wide variety of compounds. Most CYP family members are localized in the liver. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for the determination of CYP gene expression levels in the liver, we compared CYP gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, 3A7, 4A11, 4B1 and CYP27 gene expressions in PBL and in the liver by real-time reverse-transcription (RT)-PCR. We could detect expression of CYP1A1, 1A2, P1B1, 2A6, 2B6 and 2E1 genes in PBL and all the genes except for CYP2F1 in the liver. Although gene expression levels within each subfamily were closely correlated within PBL and within the liver, a clear correlation of gene expression levels between PBL and liver tissues was found only for CYP4B1. Although inter-individual variation of the expression level of each CYP gene was wide, the induced level was proportional to the basal expression level. Therefore, monitoring of CYP gene expression levels in PBL, especially those of CYP4B1, could be available as a biomarker for monitoring of exposure to environmental pollutants and assessing the associated risk. Compared with non-tumor tissue, HCC tissues tended to show overexpression of multiple CYP genes, indicating that individualized selection and more effective administration of chemotherapeutic agents could perhaps be based on the pattern of CYP overexpression. [source] Variable expression of CYP and Pgp genes in the human small intestineEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003M. Lindell Abstract Background ,The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. Methods ,The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. Results ,Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. Conclusions ,Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation. [source] Multiple P450 genes overexpressed in deltamethrin-resistant strains of Helicoverpa armigeraPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 8 2010Alexandra Brun-Barale Abstract BACKGROUND: Resistance to the pyrethroid insecticide deltamethrin has been a growing problem in the management of Helicoverpa armigera (Hübner) pest populations in West Africa. Detoxification by P450 enzymes appears to be a major mechanism of resistance, but the genes responsible for resistance are unknown. RESULTS: First, it was shown that deltamethrin resistance in strains from Burkina Faso (Kaya) and from Spain (Seville) were suppressible by piperonyl butoxide and by trichlorophenyl propynyl ether, thus indicating a major role of P450 enzyme(s) in resistance. The larval expression of 21 CYP genes encoding P450 enzymes from six CYP families were then compared by quantitative RT-PCR. Five genes, CYP4L5, CYP4L11, CYP6AE11, CYP332A1 and CYP9A14, were significantly overexpressed in the Kaya and Seville strains when compared with Heliar, a susceptible strain. Significant overexpression of multiple CYP genes (CYP4M6, CYP4M7, CYP6AE11, CYP9A12, CYP332A1 and CYP337B1) was also found in six field strains with different levels of resistance from Benin, Burkina Faso and Mali. CONCLUSION: Although functional or genetic evidence for the role of these P450s in resistance remains to be formally established, results suggest that multiple P450 enzymes contribute to deltamethrin resistance. This study is a first step towards the development of molecular tools for the detection of P450-based resistance in H. armigera. Copyright © 2010 Society of Chemical Industry [source] Gene Induction by Phenobarbital: An Update on an Old Question that Receives Key Novel Answers,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2001Laurent Corcos The drug is the representative of a myriad of lipophilic molecules able to evoke a pleiotropic response in the liver and also in prokaryotes and flies. A great deal of novel information has been obtained in recent years regarding the mechanism of cytochrome P450 (CYP) gene induction by phenobarbital. Most importantly, a nuclear orphan receptor, the constitutive androstane receptor has been identified as a primary determinant of the transcriptional activation of CYP genes in response to phenobarbital-like inducers in mammals. Another nuclear receptor, the pregnane X receptor can also mediate some of the phenobarbital response, but the functional overlap of the two inductive pathways is only partial. The response of mammalian CYP2B genes to phenobarbital was abolished in the liver of mice carrying a null allele of the constitutive androstane receptor gene, whereas that of CYP3A genes was lost in pregnane X receptor knock-out mice. [source] Cytochrome P450 gene expression levels in peripheral blood mononuclear cells in comparison with the liverCANCER SCIENCE, Issue 6 2004Motonobu Furukawa Cytochromes P450 (CYPs) compose a superfamily of similar proteins involved in detoxification and elimination, as well as activation of a wide variety of compounds. Most CYP family members are localized in the liver. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for the determination of CYP gene expression levels in the liver, we compared CYP gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, 3A7, 4A11, 4B1 and CYP27 gene expressions in PBL and in the liver by real-time reverse-transcription (RT)-PCR. We could detect expression of CYP1A1, 1A2, P1B1, 2A6, 2B6 and 2E1 genes in PBL and all the genes except for CYP2F1 in the liver. Although gene expression levels within each subfamily were closely correlated within PBL and within the liver, a clear correlation of gene expression levels between PBL and liver tissues was found only for CYP4B1. Although inter-individual variation of the expression level of each CYP gene was wide, the induced level was proportional to the basal expression level. Therefore, monitoring of CYP gene expression levels in PBL, especially those of CYP4B1, could be available as a biomarker for monitoring of exposure to environmental pollutants and assessing the associated risk. Compared with non-tumor tissue, HCC tissues tended to show overexpression of multiple CYP genes, indicating that individualized selection and more effective administration of chemotherapeutic agents could perhaps be based on the pattern of CYP overexpression. [source] Functional analysis of the cis -acting elements responsible for the induction of the Cyp6a8 and Cyp6g1 genes of Drosophila melanogaster by DDT, phenobarbital and caffeineINSECT MOLECULAR BIOLOGY, Issue 1 2010R. Morra Abstract Many Drosophila cytochrome P450 or Cyp genes are induced by caffeine and phenobarbital (PB). To understand the induction mechanism, we created Drosophila S2 cell lines stably transformed with different luciferase reporter plasmids carrying upstream DNAs of Cyp6a8 allele of the resistant 91-R strain, and the 1.1-kb upstream DNAs of Cyp6g1 of the 91-R and the susceptible 91-C strains. Following 24 h treatment with dichlorodiphenyltrichloroethane (DDT), caffeine or PB, luciferase activity of all cell lines was determined. Results showed that the 0.1-kb DNA of Cyp6a8 and the upstream DNAs of Cyp6g1 from both strains are not induced by these chemicals in S2 cells. However, the 0.2-, 0.5- and 0.8-kb DNAs of Cyp6a8 showed 13,24-, 4,5- and 2.2,2.7-fold induction with caffeine, PB and DDT, respectively. These DNAs also showed a 2,3-fold synergistic effect of caffeine and PB but not of caffeine and DDT. The results suggest that the cis -regulatory elements for all three chemicals are located within the -11/-199 DNA of Cyp6a8. Furthermore, caffeine and PB inductions appear to be mediated via different cis -elements, whereas caffeine and DDT induction may involve common regulatory elements. These stably transformed cell lines should help understand the mechanism of resistance-associated Cyp gene overexpression in Drosophila. [source] | ||||||||||