Regulation of CYP2A expression and its role in metabolism
Article Sidebar
Main Article Content
Abstract
Cytochrome P450 2A (CYP2A) plays a role in metabolism of exogenous substances including drugs and procarcinogens. This article aims to review regulatory expression of CYP2A gene and CYP2A isoforms found in human and animals, including roles of CYP2As in metabolism to obtain the overview information of CYP2A for clinical application. CYP2A6 and CYP2A13 are CYP2A expressed and showed enzyme activity in human. Both are the main enzymes in metabolism of interesting exogenous substances such as nicotine and nitrosamines procarcinogens in cigarette including high toxic and mutation induced substances. In addition, some roles of these human CYP2As are similar to mouse and rat CYP2As. Regulation of these human CYP2As involve several nuclear receptors depended on an inducer and an isoform responsible for metabolism. Moreover, roles of CYP2A depend on position and level of expression of the enzyme, by which the major responsible isoform for metabolism becomes inferior to the higher expressed isoform. Therefore, the review on regulation of CYP2A expression and its role in metabolism brings information on involvement of CYP2A and clinical significances.
Article Details
In the case that some parts are used by others The author must Confirm that obtaining permission to use some of the original authors. And must attach evidence That the permission has been included
References
Abu-Bakar A, Arthur DM, S Wikman AS, et al. Metabolism of bilirubin by human cytochrome P450 2A6. Toxicol Appl Pharmacol 2012; 261(1): 50-58.
Arpiainen S, Raffalli-Mathieu F, Lang MA, et al. Regulation of the Cyp2a5 gene involves an aryl hydrocarbon receptor-dependent pathway. Mol Pharmacol 2005; 67(4): 1325-1333.
Bbosa GS, Kitya D, Odda J, et al. Aflatoxins metabolism, effects on epigenetic mechanisms and their role in carcinogenesis. Health 2013; 5(10A): 14-34.
Bersaas A, Arnoldussen YJ, Sjøberg M, et al. Epithelial-mesenchymal transition and fox-a genes during tobacco smoke carcinogen induced transformation of human bronchial epithelial cells. Toxicol In Vitro 2016; 35: 55-65.
Bersaas ATH. FOXA genes in lung cancer in vitro and in vivo. Series of dissertations of Faculty of Medicine, University of Oslo. 2017.
Chen Y, Liu YQ, Su T, et al. Immunoblot analysis and immunohistochemical characterization of CYP2A expression in human olfactory mucosa. Biochem Pharmacol 2003; 66(7): 1245-1251.
D’Agostino J, Zhuo X, Shadid M, et al. The pneumotoxin 3-methylindole is a substrate and a mechanism-based inactivator of CYP2A13, a human cytochrome P450 enzyme preferentially expressed in the respiratory tract. Drug Metab Dispos 2009; 37(10): 2018-2027.
Dohnal V1, Wu Q, Kuča K. Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences. Arch Toxicol 2014; 88(9): 1635-1644.
Fernandez-Salguero P, Gonzalez FJ. The CYP A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis. Pharmacogenetics 1995; Spec No: S123-S128.
Fukami T, Katoh M, Yamazaki H, et al. Human cytochrome P450 2A13 efficiently metabolizes chemicals in air pollutants: naphthalene, styrene, and toluene. Chem Res Toxicol 2008; 21(3): 720-725.
He XY, Tang L, Wang SL, et al. Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract. Int J Cancer 2006; 118(11): 2665-2671.
Hoffman SM, Nelson DR, Keeney DS. Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19. Pharmacogenetics 2001; 11(8): 687-698.
Hong JY, Ding X, Smith TJ, et al. Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen, by rabbit nasal microsomes and cytochrome P450s NMa and NMb. Carcinogenesis 1992; 13(11): 2141-2144.
Ioannides C. Cytochromes P450: role in the metabolism and toxicity of drugs and other xenobiotics. Cambridge: RSC Publishing. 2008.
Itoh M, Nakajima M, Higashi E, et al. Induction of human CYP2A6 is mediated by the pregnane X receptor with peroxisome proliferator-activated receptor-gamma coactivator 1alpha. J Pharmacol Exp Ther 2006; 319(2): 693-702.
Kamataki T, Fujieda M, Kiyotani K, et al. Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk. Biochem Biophys Res Commun 2005; 338(1): 306-310.
Kobliakov V, Kulikova L, Samoilov D, et al. High expression of cytochrome P450 2a-5 (coumarin 7-hydroxylase) in mouse hepatomas. Mol Carcinog 1993; 7(4): 276-280.
Koskela S, Hakkola J, Hukkanen J, et al. Expression of CYP2A genes in human liver and extrahepatic tissues. Biochem Pharmacol 1999; 57(12): 1407-1413.
Lavery DJ, Lopez-Molina L, Margueron R, et al. Circadian expression of the steroid 15α-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP. Mol Cell Biol 1999; 19(10); 6488-6499.
Ling G, Wei Y, Ding X. Transcriptional regulation of human CYP2A13 expression in the respiratory tract by CCAAT/enhancer binding protein and epigenetic modulation. Mol Pharmacol 2007; 71(3): 807-816.
Nelson DR, Zeldin DC, Hoffman SMG, et al. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 2004; 14(1): 1-18.
Onica T, Nichols K, Larin M, et al. Dexamethasone-mediated up-regulation of human CYP2A6 involves the glucocorticoid receptor and increased binding of hepatic nuclear factor 4 alpha to the proximal promoter. Mol Pharmacol 2008; 73(2); 451-460.
Oscarson M, Gullstén H, Rautio A, et al. Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. FEBS Lett 1998; 438(3): 201-205.
Raunio H, Rahnasto-Rilla M. CYP2A6: genetics, structure, regulation, and function. Drug Metabol Drug Interact 2012; 27(2): 73-88.
Raunio H, Rautio A, Pelkonen O. The CYP2A subfamily. In C Ioannides (Ed.), Cytochromes P450. 2008: 150-177.
Robottom-Ferreira AB, Aquino SR, Queiroga R, et al. Expression of CYP2A3 mRNA and its regulation by 3-methylcholanthrene, pyrazole, and ß-ionone in rat tissues. Braz J Med Biol Res 2003; 36(7): 839-844.
Rossini A, de Almeida Simão T, Albano RM, et al. CYP2A6 polymorphisms and risk for tobacco-related cancers. Pharmacogenomics 2008; 9(11): 1737-1752.
Rowland AM, Yost GS. Selected pneumotoxic agents. In CA McQueen (Ed.), Comprehensive Toxicology. 2nd ed. 2010: 511-547.
Su T, Bao Z, Zhang QY, et al. Human cytochrome p450 cyp2a13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 2000; 60(18): 5074-5079.
Su T, Ding X. Regulation of the cytochrome P450 2A genes. Toxicol Appl Pharmacol 2004; 199(3): 285-294.
Tien ES, Negishi M. Nuclear receptors CAR and PXR in the regulation of hepatic metabolism. Xenobiotica 2006; 36(10-11): 1152-1163.
Timsit YE, Negishi M. CAR and PXR: the xenobiotic-Sensing receptors. Steroids 2007; 72(3): 231-246.
Upadhyaya P, Zimmerman CL, Hecht SS. Metabolism and pharmacokinetics of N’-nitrosonornicotine in the patas monkey. Drug Metab Dispos 2002; 30(10): 1115-1122.
von Weymarn LB, Brown KM, Murphy SE. Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism. J Pharmacol Exp Ther 2006; 316(1): 295-303.
von Weymarn LB, Murphy SE. CYP2A13-catalysed coumarin metabolism: comparison with CYP2A5 and CYP2A6. Xenobiotica 2003; 33(1): 73-81.
Weems JM, Cutler NS, Moore C, et al. 3-methylindole is mutagenic and a possible pulmonary carcinogen. Toxicol Sci 2009; 112(1): 59-67.
Wiwi CA, Gupte M, Waxman DJ. Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4α-deficient mice. Mol Endocrinol 2004; 18(8): 1975-1987.
Xiang C, Wang J, Kou X, et al. Pulmonary expression of CYP2A13 and ABCB1 is regulated by FOXA2, and their genetic interaction is associated with lung cancer. FASEB J 2015; 29(5): 1986-1998.
Xie W, Barwick JL, Simon CM, et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 2000; 14(23): 3014-3023.
Xue J, Yang S, Seng S. Mechanisms of cancer induction by tobacco-specific NNK and NNN. Cancers (Basel) 2014; 6(2): 1138-1156.
Yang X, Zhang Z, Wang X, et al. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage. Toxicol Appl Pharmacol 2013; 270(2): 114-121.
Yang XJ, Lu HY, Li ZY, et al. Cytochrome P450 2A13 mediates aflatoxin B1-induced cytotoxicity and apoptosis in human bronchial epithelial cells. Toxicology 2012; 300(3): 138-148.
Yoshinari K, Tien E, Negishi M, et al. Receptor-mediated regulation of cytochromes p450. In C Ioannides (Ed.), Cytochromes P450. 2008: 417-448.
Yuan JM, Nelson HH, Carmella SG, et al. CYP2A6 genetic polymorphisms and biomarkers of tobacco smoke constituents in relation to risk of lung cancer in the Singapore Chinese health study. Carcinogenesis 2017; 38(4): 411-418.
Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138(1): 103-141.
Zhang JY, Fen WY, Prakash C. Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab 2006; 7(8): 939-948.