Novel polymorphic human UDP-glucuronosyltransferase 2A3: Cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction

Molecular Pharmacology

Volumn 74, Issue 3, 2008, Pages 744-754

  Court, Michael H ^a,d   Hazarika, Suwagmani ^a   Krishnaswamy, Soundararajan ^a   Finel, Moshe ^b   Williams, J Andrew ^c  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF HELSINKI   (Finland)

^c PFIZER INC   (United States)

^d TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA NAPHTHOFLAVONE; BILE ACID; ENZYME VARIANT; FUROSEMIDE; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 2A3; HEPATOCYTE NUCLEAR FACTOR 1; HYODEOXYCHOLIC ACID; IBUPROFEN; IMIPRAMINE; KETOTIFEN; LAMOTRIGINE; LORAZEPAM; MESSENGER RNA; MEVINOLIN; MORPHINE; MYCOPHENOLIC ACID; NAPROXEN; NICOTINE; OXAZEPAM; PROBENECID; PROPOFOL; PROPRANOLOL; RIFAMPICIN; SALICYLIC ACID; SULFAPHENAZOLE; TRIFLUOPERAZINE; TROVAFLOXACIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

ARTICLE; BACULOVIRUS; CONTROLLED STUDY; DNA SEQUENCE; ENZYME ANALYSIS; GENE INDUCTION; GLUCURONIDATION; HUMAN; HUMAN CELL; MOLECULAR CLONING; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION;

ANIMALS; BILE ACIDS AND SALTS; CELL LINE; CLONING, MOLECULAR; CONSENSUS SEQUENCE; DEOXYCHOLIC ACID; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HEPATOCYTE NUCLEAR FACTOR 1; HOMEODOMAIN PROTEINS; HUMANS; KINETICS; LIVER; ORGAN SPECIFICITY; POLYMORPHISM, GENETIC; PROMOTER REGIONS (GENETICS); RECEPTORS, GLUCOCORTICOID; RECEPTORS, STEROID; RECOMBINANT PROTEINS; RIFAMPIN; RNA, MESSENGER;

EID: 50449083633     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.108.045500     Document Type: Article

References (38)

1. Bendtsen JD, Nielsen H, von Heijne G, and Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783-795.
2. Bock KW (2003) Vertebrate UDP-glucuronosyltransferases: functional and evolutionary aspects. Biochem Pharmacol 66:691-696.
3. Buckley DB and Klaassen CD (2007) Tissue- and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab Dispos 35:121-127.
4. Burkard I, von Eckardstein A, and Rentsch KM (2005) Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 826:147-159.
5. Caron P, Trottier J, Verreault M, Bélanger J, Kaeding J, and Barbier O (2006) Enzymatic production of bile acid glucuronides used as analytical standards for liquid chromatography-mass spectrometry analyses. Mol Pharm 3:293-302.
6. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, et al. (2003) The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res 13:2265-2270.
7. Coughtrie MW, Burchell B, Leakey JE, and Hume R (1988) The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 34:729-735.
8. Court MH (2001) Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6. J Vet Pharmacol Ther 24:415-422.
9. Court MH (2004) In vitro identification of UDP-glucuronosyltransferases (UGTs) involved in drug metabolism, in Optimization in Drug Discovery: In Vitro Methods (Yan Z and Caldwell GW eds) pp 185-202, Humana Press, Inc., Totowa, NJ.
10. Court MH (2005) Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases. Methods Enzymol 400:104-116.
11. Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, von Moltke LL, and Greenblatt DJ (2004) UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 310:656-665.
12. Court MH, Von Moltke LL, Shader RI, and Greenblatt DJ (1997) Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. Biopharm Drug Dispos 18:213-226.
13. Fournel-Gigleux S, Jackson MR, Wooster R, and Burchell B (1989) Expression of a human liver cDNA encoding a UDP-glucuronosyltransferase catalysing the glucuronidation of hyodeoxycholic acid in cell culture. FEBS Lett 243:119-122.
14. Gall WE, Zawada G, Mojarrabi B, Tephly TR, Green MD, Coffman BL, Mackenzie PI, and Radominska-Pandya A (1999) Differential glucuronidation of bile acids, androgens and estrogens by human UGT1A3 and 2B7. J Steroid Biochem Mol Biol 70:101-108.
15. Gregory PA, Lewinsky RH, Gardner-Stephen DA, and Mackenzie PI (2004) Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 genes by hepatocyte nuclear factor 1alpha and the caudal-related homeodomain protein 2. Mol Pharmacol 65:953-963.
16. Hartley DP, Dai X, He YD, Carlini EJ, Wang B, Huskey SE, Ulrich RG, Rushmore TH, Evers R, and Evans DC (2004) Activators of the rat pregnane X receptor differentially modulate hepatic and intestinal gene expression. Mol Pharmacol 65:1159-1171.
17. Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, and Court MH (2004) Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 14:225-238.
18. Heubi JE, Setchell KD, and Bove KE (2007) Inborn errors of bile acid metabolism. Semin Liver Dis 27:282-294.
19. Jedlitschky G, Cassidy AJ, Sales M, Pratt N, and Burchell B (1999) Cloning and characterization of a novel human olfactory UDP- glucuronosyltransferase. Biochem J 340:837-843.
20. Kaivosaari S, Toivonen P, Hesse LM, Koskinen M, Court MH, and Finel M (2007) Nicotine glucuronidation and the human UDP-glucuronosyltransferase UGT2B10. Mol Pharmacol 72:761-768.
21. Karlen Y, McNair A, Perseguers S, Mazza C, and Mermod N (2007) Statistical significance of quantitative PCR. BMC Bioinformatics 8:131.
22. Khurana S and Singh P (2006) Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int 26:943-948.
23. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, and Court MH (2005) UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5′-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther 313:1331-1339.
24. Lindor K (2007) Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med 357:1524-1529.
25. Mackenzie P, Little JM, and Radominska-Pandya A (2003) Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7. Biochem Pharmacol 65:417-421.
26. Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, and Nebert DW (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677-685.
27. Marschall HU, Matern H, Egestad B, Matern S, and Sjövall S (1987) 6 alpha-Glucuronidation of hyodeoxycholic acid by human liver, kidney and small bowel microsomes. Biochim Biophys Acta 921:392-397.
28. Radomińska-Pyrek A, Zimniak P, Irshaid YM, Lester R, Tephly TR, and St Pyrek J (1987) Glucuronidation of 6 alpha-hydroxy bile acids by human liver microsomes. J Clin Invest 80:234-241.
29. Rizzo G, Disante M, Mencarelli A, Renga B, Gioiello A, Pellicciari R, and Fiorucci S (2006) The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo. Mol Pharmacol 70:1164-1173.
30. Smith SA, Nagalla SR, Andrews DP, and Olsen GD (1999) Morphine regulation of a novel uridine diphosphate glucuronosyl-transferase in guinea pig pups following in utero exposure. Mol Genet Metab 68:68-77.
31. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, et al. (2001) The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 98:3369-3374.
32. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, et al. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A 99:16899-16903.
33. Tchernof A, Levesque E, Beaulieu M, Couture P, Despres JP, Hum DW, and Belanger A (1999) Expression of the androgen metabolizing enzyme UGT2B15 in adipose tissue and relative expression measurement using a competitive RT-PCR method. Clin Endocrinol (Oxf) 50:637-642.
34. Wietholtz H, Marschall HU, Sjövall J, and Matern S (1996) Stimulation of bile acid 6 alpha-hydroxylation by rifampin. J Hepatol 24:713-718.
35. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, and Evans RM (2001) An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci U S A 98:3375-3380.
36. Xie W, Yeuh MF, Radominska-Pandya A, Saini SP, Negishi Y, Bottroff BS, Cabrera GY, Tukey RH, and Evans RM (2003) Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci U S A 100:4150-4155.
37. Ye L, Liu S, Wang M, Shao Y, and Ding M (2007) High-performance liquid chromatography-tandem mass spectrometry for the analysis of bile acid profiles in serum of women with intrahepatic cholestasis of pregnancy. J Chromatogr B Analyt Technol Biomed Life Sci 860:10-17.
38. Zhang X, Zhang QY, Liu D, Su T, Weng Y, Ling G, Chen Y, Gu J, Schilling B, and Ding X (2005) Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa. Drug Metab Dispos 33:1423-1428.