Toxicological Research

  • 제27권1호
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  • Pages.25-29
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  • 2011
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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Expression of CYP2A6, CYP2D6 and CYP4A11 Polymorphisms in COS7 Mammalian Cell Line

  • Lee, Hye-Ja (College of Pharmacy, Dongguk University) ;
  • Park, Mi-Kyung (College of Pharmacy, Dongguk University) ;
  • Park, Young-Ran (College of Pharmacy, Dongguk University) ;
  • Kim, Dong-Hak (Department of Biological Sciences, Konkuk University) ;
  • Yun, Chul-Ho (School of Biological Sciences and Technology, Chonnam National University) ;
  • Chun, Young-Jin (College of Pharmacy, Chung-Ang University) ;
  • Shin, Hee-Jung (National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration) ;
  • Na, Han-Sung (National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration) ;
  • Chung, Myeon-Woo (National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration) ;
  • Lee, Chang-Hoon (College of Pharmacy, Dongguk University)
  • 투고 : 2011.01.03
  • 심사 : 2011.01.19
  • 발행 : 2011.03.01
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초록

The cytochrome P450 (P450, CYP) are the superfamily of heme-containing monooxygenase enzymes, found throughout all nature including mammals, plants, and microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a wide range of endo- and exogenous chemicals. Especially P450s involved in drug metabolisms are important for drug efficacy and polymorphisms of P450s in individuals reflect differences of drug responses between people. To study the functional differences of CYP2A6, CYP2D6, and CYP4A11 variants, we cloned the four CYP2A6, three CYP2D6, and three CYP4A11 variants, which were found in Korean populations, in mammalian expression vector pcDNA by PCR and examined their expressions in COS-7 mammalian cells using immunoblots using P450 specific polyclonal antibodies. Three of four CYP2A6, two of three CYP4A11, and two of three CYP2D6 variants showed expressions in COS-7 cells but the relative levels of expressions are remarkably different in those of each variants. Our findings may help to study and explain the differences between functions of CYP variants and drug responses in Korean populations.

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참고문헌

  1. Bandiera, S., Weidlich, S., Harth, V., Broede, P., Ko, Y. and Friedberg, T. (2005). Proteasomal degradation of human CYP1B1: effect of the Asn453Ser polymorphism on the post-translational regulation of CYP1B1 expression. Mol. Pharmacol., 67, 435-443.
  2. Cho, B.H., Park, B.L., Kim, L.H., Chung, H.S. and Shin, H.D. (2005). Highly polymorphic human CYP4A11 gene. J. Hum. Genet., 50, 259-263. https://doi.org/10.1007/s10038-005-0245-9
  3. Daly, A.K. (1995). Molecular basis of polymorphic drug metabolism. J. Mol. Med., 73, 539-553.
  4. Danielson, P.B. (2002). The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr. Drug. Metab., 3, 561-597. https://doi.org/10.2174/1389200023337054
  5. Di, Y.M., Chow, V.D., Yang, L.P. and Zhou, S.F. (2009). Structure, function, regulation and polymorphism of human cytochrome P450 2A6. Curr. Drug. Metab., 10, 754-780. https://doi.org/10.2174/138920009789895507
  6. Elbekai, R.H. and El-Kadi, A.O. (2006). Cytochrome P450 enzymes: central players in cardiovascular health and disease. Pharmacol. Ther., 112, 564-587. https://doi.org/10.1016/j.pharmthera.2005.05.011
  7. Fernandez-Salguero, P., Hoffman, S.M., Cholerton, S., Mohrenweiser, H., Raunio, H., Rautio, A., Pelkonen, O., Huang, J.D., Evans, W.E., Idle, J.R. and Gonzalez, F.J. (1995). A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. Am. J. Hum. Genet., 57, 651-660.
  8. Gainer, J.V., Bellamine, A., Dawson, E.P., Womble, K.E., Grant, S.W., Wang, Y., Cupples, L.A., Guo, C.Y., Demissie, S., O’Donnell, C.J., Brown, N.J., Waterman, M.R. and Capdevila, J.H. (2005). Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation, 111, 63-69. https://doi.org/10.1161/01.CIR.0000151309.82473.59
  9. Gardiner, S.J. and Begg, E.J. (2006). Pharmacogenetics, drugmetabolizing enzymes, and clinical practice. Pharmacol. Rev., 58, 521-590. https://doi.org/10.1124/pr.58.3.6
  10. Guengerich, F.P. (2008). Cytochrome p450 and chemical toxicology. Chem. Res. Toxicol., 21, 70-83. https://doi.org/10.1021/tx700079z
  11. Ingelman-Sundberg, M., Sim, S.C., Gomez, A. and Rodriguez-Antona, C. (2007). Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol. Ther., 116, 496-526. https://doi.org/10.1016/j.pharmthera.2007.09.004
  12. Jansson, I., Stoilov, I., Sarfarazi, M. and Schenkman, J.B. (2001). Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics, 11, 793-801. https://doi.org/10.1097/00008571-200112000-00007
  13. Kwon, J.T., Nakajima, M., Chai, S., Yom, Y.K., Kim, H.K., Yamazaki, H., Sohn, D.R., Yamamoto, T., Kuroiwa, Y. and Yokoi, T. (2001). Nicotine metabolism and CYP2A6 allele frequencies in Koreans. Pharmacogenetics, 11, 317-323. https://doi.org/10.1097/00008571-200106000-00006
  14. Lasker, J.M., Chen, W.B., Wolf, I., Bloswick, B.P., Wilson, P.D. and Powell, P.K. (2000). Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J. Biol. Chem., 275, 4118-4126. https://doi.org/10.1074/jbc.275.6.4118
  15. Lee, S.J., Lee, S.S., Jung, H.J., Kim, H.S., Park, S.J., Yeo, C.W. and Shin, J.G. (2009). Discovery of novel functional variants and extensive evaluation of CYP2D6 genetic polymorphisms in Koreans. Drug. Metab. Dispos., 37, 1464-1470. https://doi.org/10.1124/dmd.108.022368
  16. McFadyen, M.C., Melvin, W.T. and Murray, G.I. (2004). Cytochrome P450 enzymes: novel options for cancer therapeutics. Mol. Cancer. Ther., 3, 363-371.
  17. Nakajima, M., Fukami, T., Yamanaka, H., Higashi, E., Sakai, H., Yoshida, R., Kwon, J.T., McLeod, H.L. and Yokoi, T. (2006). Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin. Pharmacol. Ther., 80, 282-297. https://doi.org/10.1016/j.clpt.2006.05.012
  18. Nelson, D.R., Zeldin, D.C., Hoffman, S.M., Maltais, L.J., Wain, H.M. and Nebert, D.W. (2004). Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics, 14, 1-18. https://doi.org/10.1097/00008571-200401000-00001
  19. Owen, R.P., Sangkuhl, K., Klein, T.E. and Altman, R.B. (2009). Cytochrome P450 2D6. Pharmacogenet Genomics, 19, 559-562. https://doi.org/10.1097/FPC.0b013e32832e0e97
  20. Rodriguez-Antona, C. and Ingelman-Sundberg, M. (2006). Cytochrome P450 pharmacogenetics and cancer. Oncogene, 25, 1679-1691. https://doi.org/10.1038/sj.onc.1209377
  21. van Schaik, R.H. (2005). Cancer treatment and pharmacogenetics of cytochrome P450 enzymes. Invest New Drugs, 23, 513-522. https://doi.org/10.1007/s10637-005-4019-1
  22. Wrighton, S.A. and Stevens, J.C. (1992). The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol., 22, 1-21. https://doi.org/10.3109/10408449209145319
  23. Zanger, U.M., Raimundo, S. and Eichelbaum, M. (2004). Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol., 369, 23-37. https://doi.org/10.1007/s00210-003-0832-2
  24. Zordoky, B.N. and El-Kadi, A.O. (2010). Effect of cytochrome P450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacol. Ther., 125, 446-463. https://doi.org/10.1016/j.pharmthera.2009.12.002