Regulation of CYP2A6 protein expression by skatole, indole, and testicular steroids in primary cultured pig hepatocytes

Drug Metabolism and Disposition

Volumn 36, Issue 1, 2008, Pages 56-60

  Chen, Gang ^b   Cue, Rebecca Ayme ^a   Lundstrom, Kerstin ^b   Wood, Jeffrey D ^a   Doran, Olena ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b SWEDISH UNIVERSITY OF AGRICULTURAL SCIENCES   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTENONE; CYTOCHROME P450 2A6; ESTRONE SULFATE; INDOLE; SEX HORMONE; SKATOLE; TESTOSTERONE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DRUG METABOLISM; ENZYME ACTIVATION; ENZYME REGULATION; HORMONE INHIBITION; LIVER CELL CULTURE; LIVER METABOLISM; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SWINE;

ANDROSTENES; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BLOTTING, WESTERN; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ESTRONE; HEPATOCYTES; INDOLES; MALE; MIXED FUNCTION OXYGENASES; SKATOLE; SWINE; TESTIS; TESTOSTERONE; TESTOSTERONE CONGENERS; UP-REGULATION;

ANIMALIA; SUIDAE;

EID: 37549034662     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.107.017285     Document Type: Article

References (38)

1. Babol J, Squires EJ, and Lundström K (1998) Hepatic metabolism of skatole in pigs by cytochrome P4502E1. J Anim Sci 76:822-828.
2. Babol J, Squires EJ, and Lundström K (1999) Relationship between metabolism of androstenone and skatole in intact male pigs. J Anim Sci 77:84-92.
3. Babol J, Zamaratskaia G, Juneja G, and Lundstrom K (2004) The effect of age and distribution of skatole and indole levels in entire male pigs in four breeds: Yorkshire, Landrace, Hampshire and Duroc. Meat Sci 67:351-358.
4. Bonneau M (1982) Compounds responsible for boar taint, with special emphasis on androstenone: a review. Livest Prod Sci 9:687-707.
5. Carr BA, Ramakanth S, Daninan GA, and Yost GS (2003) Characterization of pulmonary CYP4B2, specific catalyst of methyl oxidation of 3-methylindole. Mol Pharmacol 63:1137-1147.
6. Diaz GJ and Squires EJ (2000) Metabolism of 3-methylindole by porcine liver microsomes: responsible cytochrome P450 enzymes. Toxicol Sci 55:284-292.
7. Donato MT, Vitala P, Rodriguez-Antona C, Lindfors A, Castell JV, Raunio H, Gomez Lechon MJ, and Pelkonen O (2000) CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos 28:1321-1326.
8. Doran E, Whittington FW, Wood JD, and McGivan JD (2002a) Cytochrome P450IIE1 (CYP2E1) is induced by skatole and this induction is blocked by androstenone in isolated pig hepatocytes. Chem Biol Interact 140:81-92.
9. Doran E, Whittington FM, Wood JD, and McGivan JD (2002b) The relationship between adipose tissue skatole levels, rates of hepatic microsomal skatole metabolism and hepatic cytochrome P450IIE1 expression in two breeds of pig. Anim Sci 74:461-648.
10. Endo T, Ban M, Hirata K, Yamamoto A, Hara Y, and Momose Y (2007) Involvement of CYP2A6 in the formation of a novel metabolite, 3-hydroxypilocarpine, from pilocarpine in human liver microsomes. Drug Metab Dispos 35:476-483.
11. Gillam EM, Notley LM, Cai H, De Voss JJ, and Guengerich FP (2000) Oxidation of indole by cytochrome P450 enzymes. Biochemistry 39:13817-13824.
12. Guengerich FP (1995) Human cytochrome P450 enzymes, in Cytochrome P450 (de Montello RPO ed) pp 473-535, Plenum Press, New York.
13. Horn TL, Reichert MA, Bliss RL, and Malejka-Giganti D (2002) Modulations of P450 mRNA in liver and mammary gland and P450 activities and metabolism of estrogen in liver by treatment of rats with indole-3-carbinol. Biochem Pharmacol 64:393-404.
14. Lin Z, Lou Y, and Squires EJ (2004) Molecular cloning, expression and functional characterisation of the cytochrome P450 2A6 gene in pig liver. Anim Genet 35:314-316.
15. Lin Z, Lou Y, and Squires EJ (2006) Functional polymorphism in porcine CYP2E1 gene: its association with skatole levels. J Steroid Biochem Mol Biol 99:231-237.
16. Miles JS, McLaren AW, Forrester LM, Glancey MJ, Lang MA, and Wolf CR (1990) Identification of the human liver cytochrome P-450 responsible for coumarin 7-hydroxylase activity. Biochem J 267:365-371.
17. Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R, Know JT, McLeod HL, 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.
18. Nicolau-Solano SI, McGivan JD, Whittington FM, Nieuwhof GJ, Wood JD, and Doran O (2006) Relationship between the expression of hepatic but not testicular 3β-hydroxysteroid dehydrogenase with androstenone deposition in pig adipose tissue. J Anim Sci 84:2809-2817.
19. Pearce R, Greenway D, and Parkinson A (1992) Species differences and interindivual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicumarol, and testosterone oxidation. Arch Biochem Biophys 298:211-225.
20. Pelkonen P, Lang M, and Pasanen M (1994) Tissue and sex-dependent differences in CYP2A activities in hamsters. Arch Toxicol 68:416-422.
21. Ramakanth S, Thornton-Manning JR, Wang H, Maxwell H, and Yost GS (1994) Correlation between pulmonary cytochrome P450 transcripts and the organ-selective pneumotoxicity of 3-methylindole. Toxicol Lett 71:77-85.
22. Schwenk M and Lopez del Pino V (1980) Uptake of estrogen sulfate by isolated rat liver cells. J Steroid Biochem 13:669-673.
23. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
24. Sinclair PA, Hancock S, Gilmore WJ, and Squires EJ (2005) Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes. J Steroid Biochem Mol Biol 96:79-87.
25. Skaanild MT and Friis C (1999) Cytochrome P450 sex differences in minipigs and conventional pigs. Pharmacol Toxicol 85:174-180.
26. Skaanild MT and Friis C (2005) Porcine CYP2A polymorphisms and activity. Basic Clin Pharmacol Toxicol 97:115-121.
27. Skinner TM, Anderson JA, Haley CS, and Archibald AL (2006) Assessment of SULT1A1, CYP2A6 and CYP2C18 as candidate genes for elevated backfat skatole levels in commercial and experimental pig population. Anim Genet 37:521-522.
28. Soucek P, Zuber R, Anzenbacherová E, Anzerbacher P, and Guengerich FP (2001) Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs. BMC Pharmacol 1:11-16.
29. Squires EJ and Lundström K (1997) Relationship between cytochrome P45011E1 in liver and levels of skatole and its metabolites in entire male pigs. J Anim Sci 75:2506-2511.
30. Tambyrajah WS, Doran E, Wood JD, and McGivan JD (2004) The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone. Arch Biochem Biophys 431:252-260.
31. Terner MA, Gilmore WJ, Lou Y, and Squires EJ (2006) The role of CYP2A and CYP2E1 in the metabolism of 3-methylindole in primary cultured porcine hepatocytes. Drug Metab Dispos 34:848-854.
32. Woodcroft KJ and Novak RF (1998) Xenobiotic-enhanced expression of cytochromes P450 2E1 and 2B in primary cultured rat hepatocytes. Drug Metab Dispos 26:372-378.
33. Wu D, Ramin SA, and Cederbaum AI (1997) Effect of pyridine on the expression of cytochrome P450 isozymes in primary rat hepatocytes culture. Mol Cell Biochem 173:103-111.
34. Yokoyama MT and Carlson JR (1979) Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole. Am J Clin Nutr 32:173-178.
35. Yost GS (1989) Mechanism of 3-methylindole pneumotoxicity. Chem Res Toxicol 2:273-279.
36. Zamaratskaia G, Chen G, and Lundström K (2006) Effects of sex, weight, diet and hCG administration on levels of skatole and indole in the liver and hepatic activities of cytochromes P4502E1 and P4502A6 in pigs. Meat Sci 72:331-338.
37. Zamaratskaia G, Gilmore WJ, Lundström K, and Squires EJ (2007) Effect of testicular steroids on catalytic activities of cytochrome P450 enzymes in porcine liver microsomes. Food Chem Toxicol 45:676-681.
38. Zamaratskaia G, Rydhmer L, Chen G, Madej A, Andersson HK, and Lundström K (2005) Boar taint is related to endocrine and anatomical changes at puberty but not to aggressive behaviour in entire male pigs. Reprod Domest Anim 40:500-506.