Advertisement

Cytochrome P450 in Rodents

  • Y. Funae
  • S. Imaoka
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)

Abstract

Multiple cytochrome P450 isozymes have been purified and characterized in different laboratories by various purification methods, and have been named at these different laboratories. Spectral and catalytic properties and molecular weights are not enough to distinguish between cytochrome P450 isozymes. A standardized nomenclature for cytochrome P450 has been needed for years. Since Fujii-Kuriyama et al. (1982) reported the first cDNA sequence of cytochrome P450, 154 cytochrome P450 gene names have been listed (Nebert et al. 1991) in a nomenclature system (CYP) based on the evolution of the cytochrome P450 supergene family. Purified rat cytochromes P450 have been arranged according to their cytochrome P450 gene category and extensively reviewed (Gonzalez 1989; Ryan and Levin 1990). In this chapter, we describe the purification and catalytic properties of cytochrome P450 from the rat, rabbit, and mouse and then the changes in the levels of cytochromes P450 by treatment with chemical inducers or under pathophysiological conditions.

Keywords

Lauric Acid Hepatic Microsome Cytochrome P4S0 Liver Microsomal Cytochrome Renal Microsome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bandiera S, Ryan DE, Levin W, Thomas PE (1986) Age- and sex-related expression of cytochromes P450f and P450g in rat liver. Arch Biochem Biophys 248: 658–676PubMedCrossRefGoogle Scholar
  2. Bonfils C, Larroque C, Maurel P (1986) Purification and characterization of a new form of cytochrome P-450 (LM2b) from untreated male rabbit liver microsomes. Biochem Biophys Res Commun 134: 1101–1108PubMedCrossRefGoogle Scholar
  3. Bornheim LM, Correia MA (1989) Purification and characterization of a mouse liver cytochrome P-450 induced by cannabidiol. Mol Pharmacol 36: 377–383PubMedGoogle Scholar
  4. Cheng K-C, Schenkman JB (1982) Purification and characterization of two constitutive forms of rat liver microsomal cytochrome P-450. J Biol Chem 257: 2378–2385PubMedGoogle Scholar
  5. Ding X, Pernecky SJ, Coon MJ (1991) Purification and characterization of cytochrome P450 2E2 from hepatic microsomes of neonatal rabbits. Arch Biochem Biophys 291: 270–276PubMedCrossRefGoogle Scholar
  6. Elshourbagy NA, Guzelian PS (1980) Separation, purification, and characterization of a novel form of hepatic cytochrome P-450 from rats treated with pregnenolone-16α-carbonitrile. J Biol Chem 255: 1279–1285PubMedGoogle Scholar
  7. Favreau LV, Malchoff DM, Mole JE, Schenkman JB (1987) Responses to insulin by two forms of rat hepatic microsomal cytochrome P-450 that undergo major (RLM6) and minor (RLM5b) elevations in diabetes. J Biol Chem 262: 14319–14326PubMedGoogle Scholar
  8. Fujii-Kuriyama Y, Mizukami Y, Kawajiri K, Sogawa K, Muramatsu M (1982) Primary structure of a cytochrome P-450: coding nucleotide sequence of phenobarbital-inducible cytochrome P-450 cDNA from rat liver. Proc Natl Acad Sci USA 79: 2793–2797PubMedCrossRefGoogle Scholar
  9. Funae Y, Imaoka S (1985) Simultaneous purification of multiple forms of rat liver microsomal cytochrome P-450 by high-performance liquid chromatography. Biochim Biophys Acta 842: 119–132PubMedCrossRefGoogle Scholar
  10. Funae Y, Imaoka S (1987) Purification and characterization of liver microsomal cytochrome P-450 from untreated male rats. Biochim Biophys Acta 926: 349–358PubMedCrossRefGoogle Scholar
  11. Funae Y, Imaoka S, Shimojo N (1988) Purification and characterization of diabetes-inducible cytochrome P-450. Biochem Int 16: 503–509PubMedGoogle Scholar
  12. Gonzalez FJ (1989) The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288Google Scholar
  13. Gonzalez FJ, Nebert DW, Hardwick JP, Kasper CB (1985) Complete cDNA and protein sequence of a pregnenolone 16α-carbonitrile-induced cytochrome P-450. J Biol Chem 260: 7435–7441PubMedGoogle Scholar
  14. Gonzalez FJ, Matsunaga T, Nagata K, Meyer UA, Nebert DW, Pastewka J, Kozak CA, Gillette J, Gelboin HV, Hardwick JP (1987) Debrisoquine 4-hydroxylase: characterization of a new P-450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism. DNA 6: 149–161PubMedCrossRefGoogle Scholar
  15. Guengerich FP, Dannan GA, Wright ST, Martin MV, Kaminsky LS (1982) Purification and characterization of liver microsomal cytochromes P-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or P-naphthoflavone. Biochemistry 21: 6019–6030PubMedCrossRefGoogle Scholar
  16. Harada N, Negishi M (1984a) Mouse liver testosterone 15a-hydroxylase (cytochrome P-45015(x): purification, regioselectivity, stereospecificity, and sex-dependent expression. J Biol Chem 259: 1265–1271PubMedGoogle Scholar
  17. Harada N, Negishi M (1984b) Mouse liver testosterone 16α-hydroxylase (cytochrome P-45016α): purification, regioselectivity, stereospecificity, and immunochemical characterization. J Biol Chem 259: 12285–12290PubMedGoogle Scholar
  18. Hardwick JP, Song B-J, Huberman E, Gonzalez FJ (1987) Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid ω-hydroxylase (cytochrome P-450 LAω): identification of a new cytochrome P-450 gene family. J Biol Chem 262: 801–810PubMedGoogle Scholar
  19. Heuman DM, Gallagher EJ, Barwick JL, Elshourbagy NA, Guzelian PS (1982) Immunochemical evidence for induction of a common form of hepatic cytochrome P-450 in rats treated with pregnenolone-16α-carbonitrile or other steroidal or non-steroidal agents. Mol Pharmacol 21: 753–760PubMedGoogle Scholar
  20. Holm KA, Kupfer D (1985) Isolation by ion-exchange high performance liquid chromatography of rabbit liver cytochrome P-450 with regioselectivity for ω-hydroxylation of prostaglandins. J Biol Chem 260: 2027–2030PubMedGoogle Scholar
  21. Huang M-T, West SB, Lu AYH (1976) Separation, purification, and properties of multiple forms of cytochrome P-450 from the liver microsomes of phenobarbital- treated mice. J Biol Chem 251: 4659–4665PubMedGoogle Scholar
  22. Imai Y, Sato R (1974) A gel-electrophoretically homogeneous preparation of cytochrome P-450 from liver microsomes of phenobarbital-pretreated rabbits. Biochem Biophys Res Commun 60: 8–14PubMedCrossRefGoogle Scholar
  23. Imaoka S, Funae Y (1991) Hepatic and renal cytochrome P-450s in spontaneously hypertensive rats. Biochim Biophys Acta 1074: 209–213PubMedCrossRefGoogle Scholar
  24. Imaoka S, Terano Y, Funae Y (1987a) Purification and characterization of two constitutive cytochromes P-450 (F-l and F-2) from adult female rats: identification of P-450F-1 as the phenobarbital-inducible cytochrome P-450 in male rat liver. Biochim Biophys Acta 916: 358–367PubMedCrossRefGoogle Scholar
  25. Imaoka S, Kamataki T, Funae Y (1987b) Purification and characterization of six cytochromes P-450 from hepatic microsomes of immature female rats. J Biochem (Tokyo) 102: 843–851Google Scholar
  26. Imaoka S, Shimojo N, Funae Y (1988a) Induction of renal cytochrome P-450 in hepatic microsomes of diabetic rats. Biochem Biophys Res Commun 152: 680–687PubMedCrossRefGoogle Scholar
  27. Imaoka S, Terano Y, Funae Y (1988b) Constitutive testosterone 6ß-hydroxylase in rat liver. J Biochem (Tokyo) 104: 481–487Google Scholar
  28. Imaoka S, Nagashima K, Funae Y (1990a) Characterization of three cytochrome P450s purified from renal microsomes of untreated male rats and comparison with human renal cytochrome P450. Arch Biochem Biophys 276: 473–480PubMedCrossRefGoogle Scholar
  29. Imaoka S, Terano Y, Funae Y (1990b) Changes in the amount of cytochrome P450s in rat hepatic microsomes with starvation. Arch Biochem Biophys 278: 168–178PubMedCrossRefGoogle Scholar
  30. Imaoka S, Fujita S, Funae Y (1991) Age-dependent expression of cytochrome P-450s in rat liver. Biochim Biophys Acta 1097: 187–192PubMedGoogle Scholar
  31. Ingelman-Sundberg M, Jonvall H (1984) Induction of the ethanol-inducible form of rabbit liver microsomal cytochrome P-450 by inhibitors of alcohol dehydrogenase. Biochem Biophys Res Commun 124: 375–382PubMedCrossRefGoogle Scholar
  32. Jansson I, Mole J, Schenkman JB (1985) Purification and characterization of a new form (RLM2) of liver microsomal cytochrome P-450 from untreated rat. J Biol Chem 260: 7084–7093PubMedGoogle Scholar
  33. Johnson EF (1980) Isolation and characterization of a constitutive form of rabbit liver microsomal cytochrome P-450. J Biol Chem 255: 304–309PubMedGoogle Scholar
  34. Johnson EF, Griffin KJ (1985) Variations in hepatic progesterone 21-hydroxylase activity reflect differences in the microsomal concentration of rabbit cytochrome P-450 1. Arch Biochem Biophys 237: 55–64PubMedCrossRefGoogle Scholar
  35. Kaipainen P, Nebert DW, Lang MA (1984) Purification and characterization of a microsomal cytochrome P-450 with high activity of coumarin 7-hydroxylase from mouse livers. Eur J Biochem 144: 425–431PubMedCrossRefGoogle Scholar
  36. Kamataki T, Maeda K, Yamazoe Y, Nagai T, Kato R (1983) Sex difference of cytochrome P-450 in the rat: purification, characterization, and quantitation of constitutive forms of cytochrome P-450 from liver microsomes of male and female rats. Arch Biochem Biophys 225: 758–770PubMedCrossRefGoogle Scholar
  37. Kimura S, Hardwick JP, Kozak CA, Gonzalez FJ (1989) The rat clofibrate-inducible CY P4A subfamily II. cDNA sequence of IVA3, mapping of the Cy p4a locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CY P4A genes. DNA 8: 517–525PubMedCrossRefGoogle Scholar
  38. Komori M, Imai Y, Sato R (1984) Purification and characterization of cytochrome P-450 with high affinity for 7-alkoxycoumarins. J Biochem (Tokyo) 95: 1379–1388Google Scholar
  39. Koop DR, Casazza JP (1985) Identification of ethanol-inducible P-450 isozyme 3α as the acetone and acetol monooxygenase of rabbit microsomes. J Biol Chem 260: 13607–13612PubMedGoogle Scholar
  40. Koop DR, Persson AV, Coon MJ (1981) Properties of electrophoretically homogeneous constitutive forms of liver microsomal cytochrome P-450. J Biol Chem 256:10704–10711PubMedGoogle Scholar
  41. Koop DR, Crump BL, Nordblom GD, Coon MJ (1985) Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid. Proc Natl Acad Sci USA 82: 4065–4069Google Scholar
  42. Kotake AN, Funae Y (1980) High-performance liquid chromatography technique for resolving multiple forms of hepatic membrane-bound cytochrome P-450. Proc Natl Acad Sci USA 77: 6473–6475PubMedCrossRefGoogle Scholar
  43. Kupfer D, Jansson I, Favreau LV, Theoharides AD, Schenkman JB (1988) Regioselective hydroxylation of prostaglandins by constitutive forms of cytochrome P-450 from rat liver: formation of a novel metabolite by a female- specific P-450. Arch Biochem Biophys 261: 186–195PubMedCrossRefGoogle Scholar
  44. Larrey D, Distlerath LM, Dannan GA, Wilkinson GR, Guengerich FP (1984) Purification and characterization of the rat liver microsomal cytochrome P-450 involved in the 4-hydroxylation of debrisoquine, a prototype for genetic variation in oxidative drug metabolism. Biochemistry 23: 2787–2795PubMedCrossRefGoogle Scholar
  45. Leo MA, Lieber CS (1985) New pathway for retinol metabolism in liver microsomes. J Biol Chem 260: 5228–5231PubMedGoogle Scholar
  46. Levi PE, Hodgson E (1983) Purification and reconstitution of the cytochrome P-450 monooxygenase system from uninduced mouse liver. Int J Biochem 15: 349–353CrossRefGoogle Scholar
  47. MacGeoch C, Morgan ET, Halpert J, Gustafsson J-A (1984) Purification, characterization, and pituitary regulation of the sex-specific cytochrome P-450 15ß-hydroxylase from liver microsomes of untreated female rats. J Biol Chem 259: 15433–15439PubMedGoogle Scholar
  48. McClellan-Green PD, Linko P, Yeowell HN, Goldstein JA (1989) Hormonal regulation of male-specific rat hepatic cytochrome P-450g (P-450IIC13) by androgens and the pituitary. J Biol Chem 264: 18960–18965PubMedGoogle Scholar
  49. Morgan ET, Koop DR, Coon MJ (1982) Catalytic activity of cytochrome P-450 isozyme 3α isolated from liver microsomes of ethanol-treated rabbits: oxidation of alcohols. J Biol Chem 257: 13951–13957PubMedGoogle Scholar
  50. Nagata K, Martin BM, Gillette JR, Sasame HA (1990) Isozymes of cytochrome P-450 that metabolize naphthalene in liver and lung of untreated mice. Drug Metab Dispos 18: 557–564PubMedGoogle Scholar
  51. Nebert DW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fujii-Kuriyama Y, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Loper JC, Sato R, Waterman MR, Waxman DJ (1991) The P-450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 10: 1–14PubMedCrossRefGoogle Scholar
  52. Negishi M, Nebert DW (1979) Structural gene products of the Ah locus: genetic and immunochemical evidence for two forms of mouse liver cytochrome P-450 induced by 3-methylcholanthrene. J Biol Chem 254: 11015–11023PubMedGoogle Scholar
  53. Norman RL, Johnson EF, Muller-Eberhard U (1978) Identification of the major cytochrome P-450 form transplacentally induced in neonatal rabbits by 2,3,7,8- tetrachlorodibenzo-p-dioxin. J Biol Chem 253: 8640–8647PubMedGoogle Scholar
  54. Noshiro M, Negishi M (1986) Pretranslational regulation of sex-dependent testosterone hydroxylases by growth hormone in mouse liver. J Biol Chem 261: 15923–15927PubMedGoogle Scholar
  55. Parandoosh Z, Fujita VS, Coon MJ, Philpot RM (1987) Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver: comparisons of structure and inducibility. Drug Metab Dispos 15: 59–67PubMedGoogle Scholar
  56. Ryan DE, Levin W (1990) Purification and characterization of hepatic microsomal cytochrome P-450. Pharmacol Ther 45: 153–239PubMedCrossRefGoogle Scholar
  57. Ryan DE, Thomas PE, Korzeniowski D, Levin W (1979) Separation and characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital, and 3- methylcholanthrene. J Biol Chem 254: 1365–1374PubMedGoogle Scholar
  58. Ryan DE, Thomas PE, Levin W (1982) Purification and characterization of a minor form of hepatic microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls. Arch Biochem Biophys 216: 272–288PubMedCrossRefGoogle Scholar
  59. Ryan DE, Iida S, Wood AW, Thomas PE, Lieber CS, Levin W (1984) Characterization of three highly purified cytochromes P-450 from hepatic microsomes of adult male rats. J Biol Chem 259: 1239–1250PubMedGoogle Scholar
  60. Ryan DE, Ramanathan L, Iida S, Thomas PE, Haniu M, Shively JE, Lieber CS, Levin W (1985) Characterization of a major form of rat hepatic microsomal cytochrome P-450 indue ed by isoniazid. J Biol Chem 260: 6385–6393PubMedGoogle Scholar
  61. Schenkman JB, Thummel KE, Favreau LV (1989) Physiological and pathophysiological alterations in rat hepatic cytochrome P-450. Drug Metab Rev 20: 557–584PubMedCrossRefGoogle Scholar
  62. Sonderfan AJ, Arlotto MP, Dutton DR, McMillen SK, Parkinson A (1987) Regulation of testosterone hydroxylation by rat liver microsomal cytochrome P-450. Arch Biochem Biophys 255: 27–41PubMedCrossRefGoogle Scholar
  63. Squires E, Negishi M (1988) Reciprocal regulation of sex-dependent expression of testosterone 15α-hydroxylase (P-45015) in liver and kidney of male mice by androgen: evidence for a single gene. J Biol Chem 263: 4166–4171PubMedGoogle Scholar
  64. Tanaka S, Imaoka S, Kusunose E, Kusunose M, Maekawa M, Funae Y (1990) ω- and (ω-l)-Hydroxylation of arachidonic acid, lauric acid and prostaglandin A1 by multiple forms of cytochrome P-450 purified from rat hepatic microsomes. Biochim Biophys Acta 1043: 177–181Google Scholar
  65. Thomas PE, Reik LM, Ryan DE, Levin W (1981) Regulation of three forms of cytochrome P-450 and epoxide hydrolase in rat liver microsomes: effects of age, sex, and induction. J Biol Chem 256:1044–1052PubMedGoogle Scholar
  66. Thomas PE, Reik LM, Ryan DE, Levin W (1983) Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics. J Biol Chem 258: 4590–4598PubMedGoogle Scholar
  67. Thomas PE, Bandiera S, Maines SL, Ryan DE, Levin W (1987) Regulation of cytochrome P-450j, a high-affinity N-nitrosodimethylamine demethylase, in rat hepatic microsomes. Biochemistry 26: 2280–2289PubMedCrossRefGoogle Scholar
  68. Thummel KE, Schenkman JB (1990) Effects of testosterone and growth hormone treatment on hepatic microsomal P450 expression in the diabetic rat. Mol Pharmacol 37: 119–129PubMedGoogle Scholar
  69. Thummel KE, Favreau LV, Mole JE, Schenkman JB (1988) Further characterization of RLM2 and comparison with a related form of cytochrome P-450, RLM2b. Arch Biochem Biophys 266: 319–333PubMedCrossRefGoogle Scholar
  70. van der Hoeven TA, Haugen DA, Coon MJ (1974) Cytochrome P-450 purified to apparent homogeneity from phenobarbital induced rabbit liver microsomes: catalytic activity and other properties. Biochem Biophys Res Commun 60: 569–575PubMedCrossRefGoogle Scholar
  71. Watanabe K, Narimatsu S, Yamamoto I, Yoshimura H (1991) Oxygenation mechanism in conversion of aldehyde to carboxylic acid catalyzed by a cytochrome P-450 isozyme. J Biol Chem 266: 2709–2711PubMedGoogle Scholar
  72. Waxman DJ (1984) Rat hepatic cytochrome P-450 isozyme 2c: identification as a male-specific, developmentally induced steroid 16α-hydroxylase and comparison to a female-specific cytochrome P-450 isoenzyme. J Biol Chem 259: 15481–15490PubMedGoogle Scholar
  73. Waxman DJ, Walsh C (1983) Cytochrome P-450 isozyme 1 from phenobarbital- induced rat liver: purification, characterization, and interactions with methyrapone and cytochrome b5. Biochemistry 22: 4846–4855PubMedCrossRefGoogle Scholar
  74. Waxman DJ, Ko A, Walsh C (1983) Regioselectivity and stereoselectivity of androgen hydroxylations catalyzed by cytochrome P-450 isozymes purified from phenobarbital-induced rat liver. J Biol Chem 258: 11937–11947PubMedGoogle Scholar
  75. Waxman DJ, Dannan GA, Guengerich FP (1985) Regulation of rat hepatic cytochrome P-450: age-dependent expression, hormonal imprinting, and xenobiotic inducibility of sex-specific isoenzymes. Biochemistry 24: 4409–4417PubMedCrossRefGoogle Scholar
  76. Williams DE, Hale SE, Okita RT, Masters BSS (1984) A prostaglandin ω-hydroxylase cytochrome P-450 (P-450 PG-Ω) purified from lungs of pregnant rabbits. J Biol Chem 259: 14600–14608PubMedGoogle Scholar
  77. Wolf CR, Smith BR, Ball LM, Serabjit-Singh C, Bend JR, Philpot RM (1979) The rabbit pulmonary monooxygenase system: catalytic differences between two purified forms of cytochrome P-450 in the metabolism of benzo[a]pyrene. J Biol Chem 254: 3658–3663PubMedGoogle Scholar
  78. Wolf CR, Statham CN, McMenamin MG, Bend JR, Boyd MR, Philpot RM (1982) The relationship between the catalytic activities of rabbit pulmonary cytochrome P-450 isozymes and the lung-specific toxicity of the furan derivative, 4- ipomeanol. Mol Pharmacol 22: 738–744PubMedGoogle Scholar
  79. Wood AW, Ryan DE, Thomas PE, Levin W (1983) Regio- and stereoselective metabolism of two C19 steroids by five highly purified and reconstituted rat hepatic cytochrome P-450 isozymes. J Biol Chem 258: 8839–8847PubMedGoogle Scholar
  80. Wrighton SA, Maurel P, Schuetz EG, Watkins PB, Young B, Guzelian PS (1985) Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p. Biochemistry 24: 2171–2178PubMedCrossRefGoogle Scholar
  81. Yamamoto S, Kusunose E, Ogita K, Kaku M, Ichihara K, Kusunose M (1984) Isolation of cytochrome P-450 highly active in prostaglandin w-hydroxylation from lung microsomes of rabbits treated with progesterone. J Biochem (Tokyo) 96: 593–603Google Scholar
  82. Yamazoe Y, Murayama N, Shimada M, Yamauchi K, Kato R (1989) Cytochrome P450 in livers of diabetic rats: regulation by growth hormone and insulin. Arch Biochem Biophys 268: 567–575PubMedCrossRefGoogle Scholar
  83. Yang CS, Tu YY, Koop DR, Coon MJ (1985) Metabolism of nitrosamines by purified rabbit liver cytochrome P-450 isozymes. Cancer Res 45: 1140–1145PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Y. Funae
  • S. Imaoka

There are no affiliations available

Personalised recommendations