Recent advances in P450 research

Raucy, Judy L.; Allen, Scott

doi:10.1038/sj.tpj.6500044

Cited by 41 publications

(25 citation statements)

References 60 publications

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“…The biological functions of cytochrome P450 monooxygenases are based on their ability to catalyze oxygen insertion into various compounds. Mammalian P450 proteins are critical for detoxification of PAHs and BPA (Raucy and Allen, 2001;Sasaki et al, 2005;Stiborova et al, 2003), and their catalytic functions are extremely diverse (Durst and Nelson, 1995). Thus, we speculate that upregulated WRKY genes induce the expression of cytochrome P450 genes under BPA stress by recognizing and binding special cis-elements in abiotic and biotic stress conditions.…”

Section: Arabidopsis Gene Response To Bpamentioning

confidence: 99%

Microarray analysis of differentially expressed gene responses to bisphenol A in <i>Arabidopsis </i>

Tian

Jin

et al. 2014

J. Toxicol. Sci.

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-Environmental levels of bisphenol A (BPA) are a global concern because the compound can cause damage to reproductive organs, the thyroid gland, and brain tissues at developmental stages. Plants are important in removing BPA from the atmosphere, soil, and water. However, knowledge on the mechanism by which plants respond to this compound is limited. To determine the response mechanism of plants to BPA, we used a microarray system to analyze the gene expression patterns of Arabidopsis thaliana after irrigation with 3.0 mM BPA. We identified 651 genes that were differentially expressed upregulated and 470 genes that were downregulated by BPA. These genes may specifically contribute to BPA uptake, transformation, conjugation, and compartmentation in plants. The potential function of upregulated genes in plant defense against BPA was also determined.

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Section: Arabidopsis Gene Response To Bpamentioning

confidence: 99%

Microarray analysis of differentially expressed gene responses to bisphenol A in <i>Arabidopsis </i>

Tian

Jin

et al. 2014

J. Toxicol. Sci.

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“…CYP superfamily gene products, convert procarcinogens into DNA-reactive electrophilic forms by phase I reactions [10,11]. CYP enzyme variants involve in metabolism of many different potential carcinogens as well as drugs.…”

Section: Introductionmentioning

confidence: 99%

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Sayitoğlu¹,

Hatırnaz²,

Erensoy³

et al. 2006

Am. J. Hematol.

100

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Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI ¼ 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1''null'' variants and the risk of acute leukemia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 ''null'' variants to the development of acute leukemias. Am.

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“…However, Gly91 is located within the B-B 0 helix loop at the Cterminal end of B-helix, a region which is an important part of surface channel access to heme and has previously been shown to have a profound effect on the substrate recognition in P450 proteins. [42][43][44] Furthermore, G91R substitution introduces a large charged amino acid and thus alteration of hydrophobicity, because glycine is located in a hydrophobic environment with the smallest side chain, whereas arginine has polar basic chemical groups in a much larger side chain. Table S3).…”

Section: 25mentioning

confidence: 99%

Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese

Zhou

Lin

et al. 2009

Pharmacogenomics J

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The cytochrome P450 2C19 and 2D6 enzymes are predominantly found in the human liver, and have important functions in the metabolism of many different classes of commonly used drugs. Their genetic polymorphisms give rise to both important interethnic variability in metabolism and the risk of treatment failure or dose-dependent drug toxicity. To investigate genetic polymorphisms in CYP2C19 and CYP2D6 genes in Han Chinese, we sequenced regions of the 5 0 flanking region, exon, intron and 3 0 UTR from these two genes using 100 unrelated healthy Chinese Hans. We detected 48 genetic variants in CYP2C19. A total of 15 of them are novel, including two polymorphisms in putative transcriptional factor-binding sites. The CYP2C19*1, *2, *3, *4, *17, *23, *24 and *25 alleles have frequencies of 67.5, 25.5, 2, 0.5, 3, 0.5, 0.5 and 0.5%, respectively. Based on computational predictions, three novel alleles (CYP2C19*23, *24 and *25) are deleterious mutations of the CYP2C19 protein. In CYP2D6, we identified 84 different polymorphisms, including 18 novel single-nucleotide polymorphisms. One novel polymorphism is located in a potential cis-regulatory element of the gene. The allele frequencies of CYP2D6*1, *2, *4, *5, *6, *10, *14, *21, *36, *41, *43, *52 and *71 are 18.5, 14, 1, 7, 0.5, 49, 1.5, 0.5, 1, 4, 0.5, 1 and 1.5%, respectively. The occurrence of CYP2D6 duplication is 0.5%. The novel CYP2D6*71 is anticipated as a putative poor metabolizer allele. We also performed linkage disequilibrium analysis and observed strong linkage disequilibrium spanning of the CYP2C19 and CYP2D6 regions. In addition, network analysis showed that 15 haplotypes of CYP2C19 and 22 of CYP2D6 are classified into five and three groups, respectively. Comparisons of allele frequency distributions revealed significant interethnic and intraethnic differences in these two genes. In conclusion, this study revealed that CYP2C19 and CYP2D6 have a complicated allele composition and distinct frequency distribution in Han Chinese.

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Recent advances in P450 research

Cited by 41 publications

References 60 publications

Microarray analysis of differentially expressed gene responses to bisphenol A in <i>Arabidopsis </i>

Microarray analysis of differentially expressed gene responses to bisphenol A in <i>Arabidopsis </i>

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese

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