Superfund Research Program

Antioxidant Protection by Hyperbilirubinemia in Toxicity and Disease

Project Leader: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2017

Project-Specific Links

Publications

2021

• van der Schoor LW, Verkade HJ, Bertolini A, de Wit S, Mennillo E, Rettenmeier E, Weber AA, Havinga R, Valaskova P, Jasprova J, Struik D, Bloks VW, Chen S, Schreuder AB, Vitek L, Tukey RH, Jonker JW. 2021. Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia. Sci Rep 11:11107. doi:10.1038/s41598-021-90687-5 PMID:34045606 PMCID:PMC8160219

2017

• Chen S, Lu W, Yueh MF, Rettenmeier E, Liu M, Auwerx J, Yu RT, Evans RM, Wang K, Karin M, Tukey RH. 2017. Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A 114(8):E1432-E1440. doi:10.1073/pnas.1700232114 PMID:28167773 PMCID:PMC5338369
• Hirashima R, Itoh T, Tukey RH, Fujiwara R. 2017. Prediction of drug-induced liver injury using keratinocytes. J Appl Toxicol 37:863-872. doi:10.1002/jat.3435 PMID:28138970 PMCID:PMC5500258
• Lu W, Rettenmeier E, Paszek M, Yueh MF, Tukey RH, Trottier J, Barbier O, Chen S. 2017. Crypt organoid culture as an in vitro model in drug metabolism and cytotoxicity studies. Drug Metab Dispos 45:748-754. doi:10.1124/dmd.117.075945 PMID:28468837 PMCID:PMC5478905
• Tukey RH. 2017. Mice with hyperbilirubinemia due to Gilbert's syndrome polymorphism are resistant to hepatic steatosis by decreased serine 73 phosphorylation of PPAR alpha. Am J Physiol Endocrinol Metab 312:E244-E252. doi:10.1152/ajpendo.00396.2016 PMID:28096081 PMCID:PMC5406988
• Yoda E, Paszek M, Konopnicki CM, Fujiwara R, Chen S, Tukey RH. 2017. Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress. Sci Rep 7:46489. doi:10.1038/srep46489 PMID:28422158 PMCID:PMC5395973
• Yueh MF, Chen S, Nguyen N, Tukey RH. 2017. Developmental, genetic, dietary, and xenobiotic influences on neonatal hyperbilirubinemia. Mol Pharmacol 91(5):545-553. doi:10.1124/mol.116.107524 PMID:28283555 PMCID:PMC5416747

2016

• Barateiro A, Chen S, Yueh MF, Fernandes A, Domingues HS, Relvas J, Barbier O, Nguyen N, Tukey RH, Brites D. 2016. Reduced myelination and increased glia reactivity resulting from severe neonatal hyperbilirubinemia. Mol Pharmacol 89(1):84-93. doi:10.1124/mol.115.098228 PMID:26480925 PMCID:PMC4702100
• Hirashima R, Michimae H, Takemoto H, Sasaki A, Kobayashi Y, Itoh T, Tukey RH, Fujiwara R. 2016. Induction of the UDP-glucuronosyltransferase 1A1 during the perinatal period can cause neurodevelopmental toxicity. Mol Pharmacol 90(3):265-274. doi:10.1124/mol.116.104174 PMID:27413119 PMCID:PMC4998668
• Liu M, Chen S, Yueh MF, Fujiwara R, Konopnicki CM, Hao H, Tukey RH. 2016. Cadmium and arsenic override NF-κB developmental regulation of the intestinal UGT1A1 gene and control of hyperbilirubinemia. Biochem Pharmacol 110-111:37-46. doi:10.1016/j.bcp.2016.04.003 PMID:27060662 PMCID:PMC5010383
• Liu M, Chen S, Yueh MF, Wang G, Hao H, Tukey RH. 2016. Reduction of p53 by knockdown of the UGT1 locus in colon epithelial cells causes an increase in tumorigenesis. Cell Mol Gastroenterol Hepatol 2(1):63-76.e5. doi:10.1016/j.jcmgh.2015.08.008 PMID:26807433 PMCID:PMC4721636
• Mitsugi R, Sumida K, Fujie Y, Tukey RH, Itoh T, Fujiwara R. 2016. Acyl-glucuronide as a possible cause of trovafloxacin-induced liver toxicity: Induction of chemokine (C-X-C Motif) ligand 2 by trovafloxacin acyl-glucuronide. Biol Pharm Bull 39(10):1604-1610. doi:10.1248/bpb.b16-00195 PMID:27725437
• Touboul T, Chen S, To CC, Mora-Castilla S, Sabatini K, Tukey RH, Laurent LC. 2016. Stage-specific regulation of the WNT/β-catenin pathway enhances differentiation of hESCs into hepatocytes. J Hepatol 64(6):1315-1326. doi:10.1016/j.jhep.2016.02.028 PMID:26921690 PMCID:PMC5010388
• Yueh MF, Tukey RH. 2016. Triclosan: a widespread environmental toxicant with many biological effects. Annu Rev Pharmacol Toxicol 56:251-272. doi:10.1146/annurev-pharmtox-010715-103417 PMID:26738475 PMCID:PMC4774862

2015

• Fujiwara R, Maruo Y, Chen S, Tukey RH. 2015. Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia. Toxicol Appl Pharmacol 289(1):124-132. doi:10.1016/j.taap.2015.08.018 PMID:26342858 PMCID:PMC4708261
• Kutsuno Y, Hirashima R, Sakamoto M, Ushikubo H, Michimae H, Itoh T, Tukey RH, Fujiwara R. 2015. Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity toward Endogenous Substances in Humanized UGT1 Mouse Brain. Drug Metab Dispos 43(7):1071-1076. doi:10.1124/dmd.115.063719 PMID:25953521 PMCID:PMC4468441
• Sakamoto M, Itoh T, Tukey RH, Fujiwara R. 2015. Nicotine regulates the expression of UDP-glucuronosyltransferase (UGT) in humanized UGT1 mouse brain. Drug Metab Pharmacokinet 30(4):269-275. doi:10.1016/j.dmpk.2015.04.004 PMID:26210671 PMCID:PMC4752199

2014

• Aoshima N, Fujie Y, Itoh T, Tukey RH, Fujiwara R. 2014. Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia. Sci Rep 4:6343. doi:10.1038/srep06343 PMID:25209391 PMCID:PMC4160704
• Kutsuno Y, Itoh T, Tukey RH, Fujiwara R. 2014. Glucuronidation of drugs and drug-induced toxicity in humanized UDP-glucuronosyltransferase 1 mice. Drug Metab Dispos 42(7):1146-1152. doi:10.1124/dmd.114.057083 PMID:24764149 PMCID:PMC4053997
• Maruo Y, Morioka Y, Fujito H, Nakahara S, Yanagi T, Matsui K, Mori A, Sato H, Tukey RH, Takeuchi Y. 2014. Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice. J Pediatr 165(1):36-41.e1. doi:10.1016/j.jpeds.2014.01.060 PMID:24650397 PMCID:PMC4123958
• Yueh MF, Chen S, Nguyen N, Tukey RH. 2014. Developmental onset of bilirubin-induced neurotoxicity involves Toll-like receptor 2-dependent signaling in humanized UDP-glucuronosyltransferase1 mice. J Biol Chem 289(8):4699-4709. doi:10.1074/jbc.M113.518613 PMID:24403077 PMCID:PMC3931032
• Yueh MF, Taniguchi K, Chen S, Evans RM, Hammock BD, Karin M, Tukey RH. 2014. The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proc Natl Acad Sci U S A 111(48):17200-17205. doi:10.1073/pnas.1419119111 PMID:25404284 PMCID:PMC4260592

2013

• Chen S, Yueh MF, Bigo C, Barbier O, Wang K, Karin M, Nguyen N, Tukey RH. 2013. Intestinal glucuronidation protects against chemotherapy-induced toxicity by irinotecan (CPT-11). Proc Natl Acad Sci U S A 110(47):19143-19148. doi:10.1073/pnas.1319123110 PMID:24191041 PMCID:PMC3839688
• Konopnicki CM, Dickmann LJ, Tracy JM, Tukey RH, Wienkers LC, Foti RS. 2013. Evaluation of UGT protein interactions in human hepatocytes: Effect of siRNA down regulation of UGT1A9 and UGT2B7 on propofol glucuronidation in human hepatocytes. Arch Biochem Biophys 535(2):143-149. doi:10.1016/j.abb.2013.03.012 PMID:23562620 PMCID:PMC4059507
• Sumida K, Kawana M, Kouno E, Itoh T, Takano S, Narawa T, Tukey RH, Fujiwara R. 2013. Importance of UDP-Glucuronosyltransferase 1A1 expression in skin and its induction by UVB in neonatal hyperbilirubinemias. Mol Pharmacol 84(5):679-686. doi:10.1124/mol.113.088112 PMID:23950218 PMCID:PMC3807078

2012

• Chen S, Yueh MF, Evans RM, Tukey RH. 2012. Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT 1 mice. Hepatology 56(2):658-667. doi:10.1002/hep.25671 PMID:22371261 PMCID:PMC3383890
• Fujiwara R, Chen S, Karin M, Tukey RH. 2012. Reduced expression of UGT1A1 in intestines of humanized UGT1 mice via inactivation of NF-kappa B leads to hyperbilirubinemia. Gastroenterology 142:109-U259. doi:10.1053/j.gastro.2011.09.045 PMID:21983082 PMCID:PMC3428231
• Li T, Yu RT, Atkins AR, Downes M, Tukey RH, Evans RM. 2012. Targeting the pregnane X receptor in liver injury. Expert Opin Ther Targets 16(11):1075-1083. doi:10.1517/14728222.2012.715634 PMID:22913318 PMCID:PMC4319648
• Yueh MF, Li T, Evans RM, Hammock BD, Tukey RH. 2012. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha. PLoS One 7(6):e37705. doi:10.1371/journal.pone.0037705 PMID:22761658 PMCID:PMC3376094 (Completed with ARRA Funds)

2011

• Yueh MF, Mellon PL, Tukey RH. 2011. Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor. Mol Pharmacol 79:1053-1060. doi:10.1124/mol.110.070649 PMID:21415305 PMCID:PMC3102552

2010

• Cai H, Nguyen N, Peterkin V, Yang Y, Hotz K, La Placa D, Chen S, Tukey RH, Stevens J. 2010. A humanized UGT1 mouse model expressing the UGT1A1*28 allele for assessing drug clearance by UGT1A1-dependent glucuronidation. Drug Metab Dispos 38(5):879-886. doi:10.1124/dmd.109.030130 PMID:20124398 PMCID:PMC2872941
• Fujiwara R, Nguyen N, Chen S, Tukey RH. 2010. Developmental hyperbilirubinemia and CNS toxicity in mice humanized with the UDP glucuronosyltransferase 1 (UGT1) locus. Proc Natl Acad Sci U S A 107(11):5024-5029. doi:10.1073/pnas.0913290107 PMID:20194756 PMCID:PMC2841904

2009

• Savas U, Machemer DE, Hsu M, Gaynor P, Lasker JM, Tukey RH, Johnson EF. 2009. Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J Biol Chem 284(24):16541-16552. doi:10.1074/jbc.M902074200 PMID:19366684 PMCID:PMC2713544
• Senekeo-Effenberger K, Tukey RH, Remmel RP, Larson EE, Argikar U. 2009. Studies on induction of lamotrigine metabolism in transgenic UGT1 mice. Xenobiotica 39(11):826-835. doi:10.3109/00498250903188985 PMID:19845433 PMCID:PMC2891280

2008

• Nguyen N, Bonzo JA, Chen S, Chouinard S, Kelner MJ, Hardiman G, Belanger A, Tukey RH. 2008. Disruption of the ugt1 locus in mice resembles human Crigler-Najjar type I disease. J Biol Chem 283(12):7901-7911. doi:10.1074/jbc.M709244200 PMID:18180294
• Yueh MF, Tukey RH, Chouinard S, Giton F, Fiet J, Pelletier G, Barbier O, Belanger A. 2008. Inactivation by UDP-glucuronosyltransferase enzymes: the end of androgen signaling. Psychiatr Pol 109(3-5):247-253. doi:10.1016/j.jsbmb.2008.03.016 PMID:18467088

2007

• Bonzo JA, Belanger A, Tukey RH. 2007. The role of chrysin and the Ah receptor in induction of the human UGT1A1 gene in vitro and in transgenic UGT1 mice. Hepatology 45(2):349-360. PMID:17256720
• Operana T, Nguyen N, Chen S, Beaton D, Tukey RH. 2007. Human CYP1A1GFP expression in transgenic mice serves as a biomarker for environmental toxicant exposure. Toxicol Sci 95(1):98-107. doi:10.1093/toxsci/kfl144 PMID:17065433
• Senekeo-Effenberger K, Chen S, Brace-Sinnokrak E, Bonzo JA, Yueh MF, Argikar U, Kaeding J, Trottier J, Remmel RP, Ritter JK, Barbier O, Tukey RH. 2007. Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor alpha activation. Drug Metab Dispos 35(3):419-427. doi:10.1124/dmd.106.013243 PMID:17151188
• Yueh MF, Tukey RH. 2007. Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice. J Biol Chem 282(12):8749-8758. doi:10.1074/jbc.M610790200 PMID:17259171

2005

• Bonzo JA, Chen S, Galijatovic A, Tukey RH. 2005. Arsenite inhibition of CYP1A1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin is independent of cell cycle arrest. Mol Pharmacol 67(4):1247-1256. PMID:15630080
• Chen S, Beaton D, Nguyen N, Senekeo-Effenberger K, Brace-Sinnokrak E, Argikar U, Remmel RP, Trottier J, Barbier O, Ritter JK, Tukey RH. 2005. Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem 280(45):37547-37557. doi:10.1074/jbc.M506683200 PMID:16155002
• Chen S, Operana T, Bonzo JA, Nguyen N, Tukey RH. 2005. ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem 280(6):4350-4359. doi:10.1074/jbc.M411554200 PMID:15572374
• Machemer DE, Tukey RH. 2005. The role of protein kinase C in regulation of TCDD-mediated CYP1A1 gene expression. Toxicol Sci 87(1):27-37. PMID:15947024

2004

• Galijatovic A, Beaton D, Nguyen N, Chen S, Bonzo JA, Johnson RS, Maeda S, Karin M, Guengerich FP, Tukey RH. 2004. The human CYP1A1 gene is regulated in a developmental and tissue-specific fashion in transgenic mice. J Biol Chem 279(23):23969-23976. PMID:15037607

2003

• Chen S, Nguyen N, Tamura K, Karin M, Tukey RH. 2003. The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosis. J Biol Chem 278(21):19526-19533. PMID:12637498
• Yueh MF, Huang Y, Hiller A, Chen S, Nguyen N, Tukey RH. 2003. Involvement of the xenobiotic response element (XRE) in ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1. J Biol Chem 278(17):15001-15006. PMID:12566446
• Zhang M, Sell S, Leffert HL. 2003. Hepatic progenitor cell lines from allyl alcohol-treated adult rats are derived from gamma-irradiated mouse STO cells. Stem Cells 21(4):449-458. PMID:12832698

2002

• Huang Y, Galijatovic A, Nguyen N, Geske D, Beaton D, Green J, Green M, Peters WH, Tukey RH. 2002. Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3. Pharmacogenet Genomics 12(4):287-297. PMID:12042666

2001

• Yueh MF, Nguyen N, Famourzadeh M, Strassburg CP, Oda Y, Guengerich FP, Tukey RH. 2001. The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines. Carcinogenesis 22(6):943-950. PMID:11375903