Genomes and Genes
Gene Symbol: UGT1A4
Description: UDP glucuronosyltransferase family 1 member A4
Alias: HUG-BR2, UDPGT, UDPGT 1-4, UGT-1D, UGT1-04, UGT1.4, UGT1A4S, UGT1D, UDP-glucuronosyltransferase 1-4, UDP glucuronosyltransferase 1 family, polypeptide A4, UDP glycosyltransferase 1 family, polypeptide A4, UDP-glucuronosyltransferase 1 family polypeptide A4s, UDP-glucuronosyltransferase 1-D, UDP-glucuronosyltransferase 1A4, bilirubin UDP-glucuronosyltransferase isozyme 2, bilirubin-specific UDPGT isozyme 2
Publications127 found, 100 shown here
- Yamashita Y, Ueyama T, Nishi T, Yamamoto Y, Kawakoshi A, Sunami S, et al. Nrf2-inducing anti-oxidation stress response in the rat liver--new beneficial effect of lansoprazole. PLoS ONE. 2014;9:e97419 pubmed publisher..e. the AhR/Cyp1a1/Nrf2 pathway in hepatocytes. ..
- Böhmdorfer M, Szakmary A, Schiestl R, Vaquero J, Riha J, Brenner S, et al. Involvement of UDP-Glucuronosyltransferases and Sulfotransferases in the Excretion and Tissue Distribution of Resveratrol in Mice. Nutrients. 2017;9: pubmed publisher..In summary, our data revealed organ-specific expression of Sults and Ugts in mice that strongly affects resveratrol concentrations; this may also be predictive in humans following oral uptake of dietary resveratrol. ..
- Crespo M, Sole M. The use of juvenile Solea solea as sentinel in the marine platform of the Ebre Delta: in vitro interaction of emerging contaminants with the liver detoxification system. Environ Sci Pollut Res Int. 2016;23:19229-36 pubmed publisher..and BFCOD, carboxylesterase (CbE), glutathione S-transferase (GST) and uridine diphosphate glucuronyltransferase (UDPGT); and oxidative stress parameters such as catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (..
- Girard Bock C, Benoit Biancamano M, Villeneuve L, Desjardins S, Guillemette C. A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. Drug Metab Dispos. 2016;44:1867-1871 pubmed..Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. ..
- Wang C, Saar V, Leung K, Chen L, Wong G. Human amyloid ? peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans. Neurobiol Dis. 2018;109:88-101 pubmed publisher..Taken together, our C. elegans double transgenic model provides insight on the fundamental neurobiologic processes underlying human AD and recapitulates selected transcriptomic changes observed in human AD brains. ..
- Liu J, Zhou Z, Zhang W, Bell M, Waalkes M. Changes in hepatic gene expression in response to hepatoprotective levels of zinc. Liver Int. 2009;29:1222-9 pubmed publisher..Such gene expression changes, particularly the dramatic induction of MT and Nrf2 antioxidant pathway, occur in the absence of overt liver injury, and are probably important in the hepatoprotective effects of Zn against toxic insults. ..
- Hu D, Mackenzie P, Lu L, Meech R, McKinnon R. Induction of human UDP-Glucuronosyltransferase 2B7 gene expression by cytotoxic anticancer drugs in liver cancer HepG2 cells. Drug Metab Dispos. 2015;43:660-8 pubmed publisher..g., epirubicin) and noncytotoxic drugs (e.g., morphine), which are UGT2B7 substrates. ..
- Hultman M, Song Y, Tollefsen K. 17Î±-Ethinylestradiol (EE2) effect on global gene expression in primary rainbow trout (Oncorhynchus mykiss) hepatocytes. Aquat Toxicol. 2015;169:90-104 pubmed publisher..In conclusion, global transcriptional analysis demonstrated that EE2 affected a number of toxicologically relevant pathways associated with an estrogenic MoA in the rainbow trout hepatocytes. ..
- Coltell O, Asensio E, Sorli J, Barragán R, Fernández Carrión R, Portoles O, et al. Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population. Nutrients. 2019;11: pubmed publisher..In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. ..
- Ramprasath T, Selvam G. Potential impact of genetic variants in Nrf2 regulated antioxidant genes and risk prediction of diabetes and associated cardiac complications. Curr Med Chem. 2013;20:4680-93 pubmed..Thus, the present review aims to explore the relationship between free radicals, diabetes and its associated complications with respect to the genetic makeup of Nrf2/ARE regulated genes in an effort to expand treatment options. ..
- Saengtienchai A, Ikenaka Y, Kawata M, Kawai Y, Takeda K, Kondo T, et al. Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species. Comp Biochem Physiol C Toxicol Pharmacol. 2018;214:28-35 pubmed publisher..Characterization of xenobiotic metabolism revealed species differences between birds and mammals, raising concerns about exposure to various xenobiotics in the environment. ..
- Tsai M, Wang Y, Lai Y, Tsou H, Liou G, Ko J, et al. Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice. Toxicol Lett. 2018;290:97-109 pubmed publisher..These data suggested that kaempferol protects the liver against propacetamol-induced injury through anti-oxidative, anti-inflammatory and anti-apoptotic activities. ..
- Zhang C, Pang Y, Zhang Q, Huang G, Xu M, Tang B, et al. Hemolymph transcriptome analysis of Chinese mitten crab (Eriocheir sinensis) with intact, left cheliped autotomy and bilateral eyestalk ablation. Fish Shellfish Immunol. 2018;81:266-275 pubmed publisher..Our research obtained abundant E. sinensis hemolymph transcriptome information by RNA-Seq, which provides multi-level information for the cloning of novel genes and the study of hemolymph molecular immunology mechanisms of E. sinensis. ..
- Zhu Y, Liu W, Qi S, Wang H, Wang Y, Deng G, et al. Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo. Eur J Pharm Sci. 2018;123:459-474 pubmed publisher..The d-VAS might be the dominant configuration for treating Alzheimer's disease. ..
- SolÃ© M, Fortuny A, MaÃ±anÃ³s E. Effects of selected xenobiotics on hepatic and plasmatic biomarkers in juveniles of Solea senegalensis. Environ Res. 2014;135:227-35 pubmed publisher..reductases, carboxylesterases (CbEs) and the conjugation enzyme uridine diphosphate glucuronyltransferase (UDPGT)...
- Iwamura A, Watanabe K, Akai S, Nishinosono T, Tsuneyama K, Oda S, et al. Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice. Drug Metab Dispos. 2016;44:888-96 pubmed publisher..This is the first study to demonstrate that AG accumulation in the kidney by TOTP and BSO treatment could explain renal toxicity and to show the in vivo toxicological potential of AGs. ..
- Dong S, Ji J, Hu L, Wang H. Dihydromyricetin alleviates acetaminophen-induced liver injury via the regulation of transformation, lipid homeostasis, cell death and regeneration. Life Sci. 2019;: pubmed publisher..Based on these findings, DHM provides a potential and novel approach for preventing and treating APAP-induced liver damage, and SREBP-1c signalling might be a new therapeutic target for APAP hepatotoxicity. ..
- Szultka Mlynska M, Buszewski B. Study of in-vitro metabolism of selected antibiotic drugs in human liver microsomes by liquid chromatography coupled with tandem mass spectrometry. Anal Bioanal Chem. 2016;408:8273-8287 pubmed..Finally, LC-MS/MS spectrometry was revealed to be a suitable analytical tool to procure a feasible analytical base for the envisioned in vivo experiments. Graphical Abstract Workflow overview of in vitro drug metabolism studies. ..
- Li Q, Wang L, Dai P, Zeng X, Qi X, Zhu L, et al. A combined strategy of mass fragmentation, post-column cobalt complexation and shift in ultraviolet absorption spectra to determine the uridine 5'-diphospho-glucuronosyltransferase metabolism profiling of flavones after oral administration of a flavo. J Chromatogr A. 2015;1395:116-28 pubmed publisher..4h, except for the concentration of luteolin 3'-glucronide (approximately 9h). Rat exposure was practically non-linear under the studied dosages (200 to 400mg/kg). ..
- Magdalou J, Totis M, Boiteux Antoine A, Fournel Gigleux S, Siest G, Schladt L, et al. Effect of 1-benzylimidazole on cytochromes P-450 induction and on the activities of epoxide hydrolases and UDP-glucuronosyltransferases in rat liver. Biochem Pharmacol. 1988;37:3297-304 pubmed..These observations emphasize the variety of the effects of 1-benzylimidazole on drug-metabolizing enzymes. ..
- Talavera Pons S, Boyer A, Lamblin G, Chennell P, Châtenet F, Nicolas C, et al. Managing drug-drug interactions with new direct-acting antiviral agents in chronic hepatitis C. Br J Clin Pharmacol. 2017;83:269-293 pubmed publisher..The key to interpret DDI data is a good understanding of the pharmacokinetic profiles of the drugs involved. Their ability to inhibit CYP450-3A4 and transporters (hepatic and/or intestinal) can have significant clinical consequences...
- Chen S, Tukey R. Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos. 2018;46:1745-1755 pubmed publisher..Our findings outline a new model that includes an active intestinal ROS /IκB kinase/nuclear receptor corepressor 1 loop that can be applied to an understanding of breast milk-induced jaundice. ..
- Huang C, Chen H, Lin T, Lin A, Lii C. Shikonin upregulates the expression of drug-metabolizing enzymes and drug transporters in primary rat hepatocytes. J Ethnopharmacol. 2018;216:18-25 pubmed publisher..Moreover, Nrf2 activation is dependent on mitogen-activated protein kinases. ..
- Cai S, Hou N, Zhao G, Liu X, He Y, Liu H, et al. Nrf2 Is a Key Regulator on Puerarin Preventing Cardiac Fibrosis and Upregulating Metabolic Enzymes UGT1A1 in Rats. Front Pharmacol. 2018;9:540 pubmed publisher..Autoregulatory circuits between puerarin and Nrf2-regulated UGT1A1 attenuates side effects associated with treatment, but it does not weaken puerarin's pharmacological effects. ..
- Kabeya T, Qiu S, Hibino M, Nagasaki M, Kodama N, Iwao T, et al. Cyclic AMP Signaling Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Intestinal Epithelial Cells. Drug Metab Dispos. 2018;46:1411-1419 pubmed publisher..This study is the first to report that the activation of cAMP signaling promotes differentiation of human iPS cell-derived intestinal epithelial cells. ..
- Greer A, Dates C, Starlard Davenport A, Edavana V, Bratton S, Dhakal I, et al. A potential role for human UDP-glucuronosyltransferase 1A4 promoter single nucleotide polymorphisms in the pharmacogenomics of tamoxifen and its derivatives. Drug Metab Dispos. 2014;42:1392-400 pubmed publisher..Recombinant UGT1A4 catalyzed the formation of N-glucuronides of Tam and its derivatives and was the most active UGT enzyme toward ..
- Papageorgiou I, Freytsis M, Court M. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver. Biochem Pharmacol. 2016;117:78-87 pubmed publisher..Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. ..
- Shi X, Zhang G, Mackie B, Yang S, Wang J, Shan L. Comparison of the in vitro metabolism of psoralidin among different species and characterization of its inhibitory effect against UDP- glucuronosyltransferase (UGT) or cytochrome p450 (CYP450) enzymes. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1029-1030:145-156 pubmed publisher..CYP2C19 played a key role in the metabolism of psorslidin in human liver microsomes. These findings could be used to advance the understanding of psoralidin. ..
- Iwamura A, Nakajima M, Oda S, Yokoi T. Toxicological potential of acyl glucuronides and its assessment. Drug Metab Pharmacokinet. 2017;32:2-11 pubmed publisher..In addition to in vitro studies, studies in model animals indicate the in vivo toxicological potential of AGs and help understand the mechanisms of the AG toxicity. ..
- Nomura A, Maruo Y, Taga T, Takeuchi Y. Contribution of UGT1A1 variations to chemotherapy-induced unconjugated hyperbilirubinemia in pediatric leukemia patients. Pediatr Res. 2016;80:252-7 pubmed publisher..Therefore, it is not necessary to cease chemotherapy in patients with these mutations who develop unconjugated hyperbilirubinemia without associated liver dysfunction. ..
- Vrzal R, Illes P, Dvorak Z. Transplant drugs affect the expression of phase II and antioxidant enzymes in human carcinoma cells HepG2 but not in primary cultures of human hepatocytes: In vitro comparative study. Pharmacol Rep. 2016;68:1008-14 pubmed publisher..On the other hand, Mycophenolate mofetil induced GPX1 mRNA, although it suppressed mRNA level of UGT1A4/1A9/2B7/2B10, GSTA1/O1/T1, GSR and HMOX1 in HepG2 cells...
- He C, Zhang G, Zhang J, Zeng Y, Liu J. Integrated analysis of multiomic data reveals the role of the antioxidant network in the quality of sea buckthorn berry. FASEB J. 2017;31:1929-1938 pubmed publisher..He, C., Zhang, G., Zhang, J., Zeng, Y., Liu, J. Integrated analysis of multiomic data reveals the role of the antioxidant network in the quality of sea buckthorn berry. ..
- Achour B, Dantonio A, Niosi M, Novak J, Al Majdoub Z, Goosen T, et al. Data Generated by Quantitative Liquid Chromatography-Mass Spectrometry Proteomics Are Only the Start and Not the Endpoint: Optimization of Quantitative Concatemer-Based Measurement of Hepatic Uridine-5'-Diphosphate-Glucuronosyltransferase Enzymes wit. Drug Metab Dispos. 2018;46:805-812 pubmed publisher..The proposed strategy offers significant improvement on existing guidelines applicable to clinically relevant proteins quantified using QconCAT. ..
- Anderson G, Peterson T, Vonder Haar C, Farin F, Bammler T, MacDonald J, et al. Effect of Traumatic Brain Injury, Erythropoietin, and Anakinra on Hepatic Metabolizing Enzymes and Transporters in an Experimental Rat Model. AAPS J. 2015;17:1255-67 pubmed publisher..In conclusion, EPO treatment may result in a significant decrease in the metabolism of Cyp-metabolized drugs. In contrast to clinical TBI, there was not a significant effect of experimental TBI on CYP or UGT metabolic enzymes. ..
- Wijayakumara D, Hu D, Meech R, McKinnon R, Mackenzie P. Regulation of Human UGT2B15 and UGT2B17 by miR-376c in Prostate Cancer Cell Lines. J Pharmacol Exp Ther. 2015;354:417-25 pubmed publisher..This represents the first evidence for post-transcriptional regulation of UGT2B15 and UGT2B17 by miRNAs in prostate cancer cells and may have importance in regulating androgen receptor signaling. ..
- Benton M, Lea R, Macartney Coxson D, Bellis C, Carless M, Curran J, et al. Serum bilirubin concentration is modified by UGT1A1 haplotypes and influences risk of type-2 diabetes in the Norfolk Island genetic isolate. BMC Genet. 2015;16:136 pubmed publisher..GWAS of blood-based clinical traits in the Norfolk Island population has identified variants within the UDPGT family directly associated with serum bilirubin levels, which is in turn implicated with reduced risk of ..
- He Y, Folkerts E, Zhang Y, Martin J, Alessi D, Goss G. Effects on Biotransformation, Oxidative Stress, and Endocrine Disruption in Rainbow Trout (Oncorhynchus mykiss) Exposed to Hydraulic Fracturing Flowback and Produced Water. Environ Sci Technol. 2017;51:940-947 pubmed publisher..The increased expression of cyp1a (2.49 ± 0.28-fold), udpgt (2.01 ± 0.31-fold), sod (1.67 ± 0.09-fold), and gpx (1.58 ± 0.10-fold) in raw sample exposure group (7...
- Xu S, Liu L, Chen Y, Liu M, Lu T, Wang H, et al. Population pharmacokinetics of lamotrigine co-administered with valproic acid in Chinese epileptic children using nonlinear mixed effects modeling. Eur J Clin Pharmacol. 2018;74:583-591 pubmed publisher..and to investigate the effects of valproic acid (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4, UGT2B7) on the pharmacokinetics of LTG...
- You B, Gong E, Choi Y. Inhibitory Effect of Sauchinone on UDP-Glucuronosyltransferase (UGT) 2B7 Activity. Molecules. 2018;23: pubmed publisher..Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations. ..
- ..Clinical effects of this genotype-based dosing recommendation is currently prospectively being investigated. Overall, the data suggest that UGT1A1 genotyping is useful for improving belinostat therapy. ..
- Inoue K, Yamamoto Y, Suzuki E, Takahashi T, Umemura A, Takahashi Y, et al. Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy. Eur J Clin Pharmacol. 2016;72:555-62 pubmed publisher..phenytoin co-administration, and the co-administration of phenobarbital and/or carbamazepine as well as UGT1A4 142T>G and UGT2B7 -161C>T polymorphisms (adjusted coefficients of determination R (2) = 0.734)...
- Rouleau M, Audet Delage Y, Desjardins S, Rouleau M, Girard Bock C, Guillemette C. Endogenous Protein Interactome of Human UDP-Glucuronosyltransferases Exposed by Untargeted Proteomics. Front Pharmacol. 2017;8:23 pubmed publisher..Our work provides unprecedented evidence for a functional interaction between glucuronidation and bioenergetic metabolism. ..
- Banerjee Dixit A, Sharma D, Srivastava A, Banerjee J, Tripathi M, Prakash D, et al. Upregulation of breast cancer resistance protein and major vault protein in drug resistant epilepsy. Seizure. 2017;47:9-12 pubmed publisher..1(MRP1), major vault protein (MVP), breast cancer resistance protein (BCRP), and one drug metabolising enzyme (UGT1A4) as compared to non-epileptic controls which were tissues resected from tumor periphery (n=6) and autopsy tissues (..
- Kahma H, Filppula A, Neuvonen M, Tarkiainen E, Tornio A, Holmberg M, et al. Clopidogrel Carboxylic Acid Glucuronidation is Mediated Mainly by UGT2B7, UGT2B4, and UGT2B17: Implications for Pharmacogenetics and Drug-Drug Interactions . Drug Metab Dispos. 2018;46:141-150 pubmed publisher..The formation of clopidogrel acyl-β-d-glucuronide is impaired in carriers of the UGT2B17 deletion. These findings may have implications regarding the intracellular mechanisms leading to CYP2C8 inactivation by clopidogrel. ..
- Papageorgiou I, Court M. Identification and validation of microRNAs directly regulating the UDP-glucuronosyltransferase 1A subfamily enzymes by a functional genomics approach. Biochem Pharmacol. 2017;137:93-106 pubmed publisher..Finally, miR-21-3p and miR-200a-3p expression were negatively correlated with UGT1A6 activity and mRNA in human liver samples. Thus, UGT1A is regulated by multiple miRNAs with some showing allele-dependent effects. ..
- Matic M, de Wildt S, Tibboel D, van Schaik R. Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice. Clin Chem. 2017;63:1204-1213 pubmed publisher..The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context. ..
- Isobe T, Ohkawara S, Ochi S, Tanaka Kagawa T, Jinno H, Hanioka N. Naringenin glucuronidation in liver and intestine microsomes of humans, monkeys, rats, and mice. Food Chem Toxicol. 2018;111:417-422 pubmed publisher..These results suggest that the metabolic abilities and regioselectivity of UGT enzymes toward naringenin in the liver and intestines generally differ between primates and rodents. ..
- Hanioka N, Isobe T, Kinashi Y, Tanaka Kagawa T, Jinno H. Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions. Arch Toxicol. 2016;90:1651-7 pubmed publisher
- Ishimaru S, Yuza Y, Kaneko T, Urashima M. Effect of UGT2B17 deletion polymorphism on prognosis in pediatric cancer. Pediatr Int. 2017;59:427-431 pubmed publisher..0004). UGT2B17 deletion polymorphism may improve the relapse-free rate in children with non-lymphoblastic malignancy. ..
- Ran R, Zhang C, Li R, Chen B, Zhang W, Zhao Z, et al. Evaluation and Comparison of the Inhibition Effect of Astragaloside IV and Aglycone Cycloastragenol on Various UDP-Glucuronosyltransferase (UGT) Isoforms. Molecules. 2016;21: pubmed..034 μM and 20.98 μM, respectively. ..
- Liu X, Sheng L, Zhao M, Mi J, Liu Z, Li Y. In vitro glucuronidation of the primary metabolite of 10-chloromethyl-11-demethyl-12-oxo-calanolide A by human liver microsomes and its interactions with UDP-glucuronosyltransferase substrates. Drug Metab Pharmacokinet. 2015;30:89-96 pubmed publisher..As a result, UGT1A1 was the major isozyme responsible for the glucuronidation of M3, followed by UGT1A4, UGT1A9 and UGT2B7...
- Chen L, Yu M, Wu Q, Peng Z, Wang D, Kuca K, et al. Gender and geographical variability in the exposure pattern and metabolism of deoxynivalenol in humans: a review. J Appl Toxicol. 2017;37:60-70 pubmed publisher..In this review, we provide global information on DON metabolism, human exposure and gender differences in humans. Also, control strategies for this mycotoxin are discussed. Copyright © 2016 John Wiley & Sons, Ltd...
- Cheng Y, Zhou J, Wang M, Liu Y, Guo B, Chen B. Single-shot multi-reaction monitoring of intact marker conjugates for quantitative profiling of human major microsomal glucuronidations and its utility to screen inhibitors from medicinal herbs. Anal Bioanal Chem. 2016;408:8117-8132 pubmed..Graphical abstract Multi-reaction monitoring of intact conjugate metabolites for quantitative profiling of human major glucuronidations. ..
- Gu B, Laborda P, Wei S, Duan X, Song H, Liu L, et al. Discovery and Biochemical Characterization of the UDP-Xylose Biosynthesis Pathway in Sphaerobacter thermophilus. Protein Pept Lett. 2016;23:1103-1110 pubmed..The biosynthetic potential of StUGD was further exemplified in a coupled enzymatic reaction with an UDP-glucuronosyltransferase, allowing the glucuronylation of the natural model substrate bilirubin. ..
- Ikuta H, Kawase A, Iwaki M. Stereoselective Pharmacokinetics and Chiral Inversion of Ibuprofen in Adjuvant-induced Arthritic Rats. Drug Metab Dispos. 2017;45:316-324 pubmed publisher..These results suggested that AA could affect drug efficacies after stereoselective changes in the pharmacokinetics of R-IB and S-IB. ..
- Miners J, Chau N, Rowland A, Burns K, McKinnon R, Mackenzie P, et al. Inhibition of human UDP-glucuronosyltransferase enzymes by lapatinib, pazopanib, regorafenib and sorafenib: Implications for hyperbilirubinemia. Biochem Pharmacol. 2017;129:85-95 pubmed publisher..IC50 values for the inhibition of all UGT1A enzymes, except UGT1A3 and UGT1A4, by the four KIs were <10?M...
- Dluzen D, Sutliff A, Chen G, Watson C, Ishmael F, Lazarus P. Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines. J Pharmacol Exp Ther. 2016;359:182-93 pubmed publisher..This is the first evidence that miRNAs regulate UGT 2B7, 2B4, and 2B10 expression, and that miR-216b-5p regulation of UGT2B proteins may be important in regulating the metabolism of UGT2B substrates. ..
- Kaku T, Ogura K, Nishiyama T, Ohnuma T, Muro K, Hiratsuka A. Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol. 2004;67:2093-102 pubmed..02 )) was observed in the activities between 7-hydroxy-4-(trifluoromethyl)coumarin and TAM. Only UGT1A4 catalyzed the N-linked glucuronidation of TAM among recombinant UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, ..
- Cao Y, Du Z, Zhu Z, Sun H, Fu Z, Yang K, et al. Inhibitory effects of fifteen phthalate esters in human cDNA-expressed UDP-glucuronosyltransferase supersomes. Chemosphere. 2017;185:983-990 pubmed publisher..In conclusion, exposure to PAEs might influence the metabolic elimination of endogenous compounds and xenobiotics through inhibiting UGTs. ..
- Ritter J, Chen F, Sheen Y, Tran H, Kimura S, Yeatman M, et al. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem. 1992;267:3257-61 pubmed..With an understanding of the gene structure, lethal, as well as the nonlethal defects, associated with bilirubin transferase activity can now be determined. ..
- Moghrabi N, Clarke D, Boxer M, Burchell B. Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. Genomics. 1993;18:171-3 pubmed
- Ehmer U, Vogel A, Schütte J, Krone B, Manns M, Strassburg C. Variation of hepatic glucuronidation: Novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology. 2004;39:970-7 pubmed..the blood of 363 subjects (128 patients with HCC, 235 blood donors) was analyzed for polymorphisms of the UGT1A3, UGT1A4, UGT1A8, UGT1A9, UGT1A10 genes using polymerase chain reaction, sequencing analysis...
- Berkhout M, Roelofs H, te Morsche R, Dekker E, van Krieken J, Nagengast F, et al. Detoxification enzyme polymorphisms are not involved in duodenal adenomatosis in familial adenomatous polyposis. Br J Surg. 2008;95:499-505 pubmed..of uridine 5'-diphosphate glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs): UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A10, UGT2B4, UGT2B7, UGT2B15, GSTA1, GSTP1, GSTM1 and GSTT1...
- Yu B, Zheng Y, Alexander D, Morrison A, Coresh J, Boerwinkle E. Genetic determinants influencing human serum metabolome among African Americans. PLoS Genet. 2014;10:e1004212 pubmed publisher..These results highlight the value of using endophenotypes proximal to gene function to discover new insights into biology and disease pathology. ..
- Xu M, Dong P, Tian X, Wang C, Huo X, Zhang B, et al. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction. Pharmacol Res. 2016;110:139-150 pubmed publisher..A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro...
- Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, et al. Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun. 1993;197:1239-44 pubmed..Two bilirubin UGT isozymes, UGT1A and UGT1D, have been identified...
- Operaña T, Tukey R. Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation. J Biol Chem. 2007;282:4821-9 pubmed..This technique demonstrated that UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 self-oligomerize (homodimerize)...
- Kawase A, Ito A, Yamada A, Iwaki M. Age-related changes in mRNA levels of hepatic transporters, cytochrome P450 and UDP-glucuronosyltransferase in female rats. Eur J Drug Metab Pharmacokinet. 2015;40:239-44 pubmed publisher..This study showed that aging affected the mRNA expression of hepatic transporters and metabolic enzymes in rats. ..
- Lu D, Xie Q, Wu B. N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification. J Pharm Biomed Anal. 2017;145:692-703 pubmed publisher..This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N-glucuronidation are not fully clear...
- Hiller A, Nguyen N, Strassburg C, Li Q, Jainta H, Pechstein B, et al. Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999;27:605-12 pubmed..From the known substrate specificities of UGT1A4 toward lamotrigine and bilirubin and our activity and inhibition data, we conclude that UGT1A4 is a major ..
- Gulcebi M, Ozkaynakcı A, Goren M, Aker R, Ozkara C, Onat F. The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy. Epilepsy Res. 2011;95:1-8 pubmed publisher..In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels ..
- Labad J, Martorell L, Huerta Ramos E, Cobo J, Vilella E, Rubio Abadal E, et al. Pharmacogenetic study of the effects of raloxifene on negative symptoms of postmenopausal women with schizophrenia: A double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2016;26:1683-9 pubmed publisher..In conclusion, our study suggests that genetic variants in UGT1A8 and ESR1 genes modulate the treatment response to adding raloxifene to antipsychotic treatment in postmenopausal women with schizophrenia. ..
- Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, et al. Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013;41:1389-97 pubmed publisher..These are drugs that were previously reported to be substrates for UGT1A4 or UGT1A3, and that contain in their structure either tertiary aliphatic amines, cyclic amines, or an imidazole ..
- Wang Z, Wong T, Hashizume T, Dickmann L, Scian M, Koszewski N, et al. Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3: metabolite structure, kinetics, inducibility, and interindividual variability. Endocrinology. 2014;155:2052-63 pubmed publisher..Two isozymes, UGT1A4 and UGT1A3, were identified as the principal catalysts of 25OHD3 glucuronidation in human liver...
- Zhou J, Argikar U, Remmel R. Functional analysis of UGT1A4(P24T) and UGT1A4(L48V) variant enzymes. Pharmacogenomics. 2011;12:1671-9 pubmed publisherTo investigate the effects of two nonsynonymous SNPs, UGT1A4*2 (rs#: 6755571, 70C>A, P24T) and UGT1A4*3 (rs#: 2011425, 142T>G, L48V), on the function of UGT1A4 against dihydrotestosterone (DHT), transandrosterone (t-AND), ..
- Reese M, Savina P, Generaux G, Tracey H, Humphreys J, Kanaoka E, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013;41:353-61 pubmed publisher..These in vitro studies demonstrate a low propensity for DTG to be a perpetrator of clinical drug interactions and provide a basis for predicting when other drugs could result in a drug interaction with DTG...
- Lu L, Zhou J, Shi J, Peng X, Qi X, Wang Y, et al. Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients. PLoS ONE. 2015;10:e0127524 pubmed publisher..In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-..
- Yagura H, Watanabe D, Kushida H, Tomishima K, Togami H, Hirano A, et al. Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1. BMC Infect Dis. 2017;17:622 pubmed publisher..Our results also suggest a relationship between plasma DTG trough concentrations and NP-AEs, and that carrying UGT1A1*6 and/or UGT1A1*28 alleles might be a risk factor for NP-AEs. ..
- Zhou J, Tracy T, Remmel R. Glucuronidation of dihydrotestosterone and trans-androsterone by recombinant UDP-glucuronosyltransferase (UGT) 1A4: evidence for multiple UGT1A4 aglycone binding sites. Drug Metab Dispos. 2010;38:431-40 pubmed publisher..Although atypical kinetic profiles (nonhyperbolic, non-Michaelis-Menten) of UGT1A4-catalyzed glucuronidation have been reported occasionally, systematic kinetic studies to explore the existence of ..
- Gagez A, Rouguieg Malki K, Sauvage F, Marquet P, Picard N. Simultaneous evaluation of six human glucuronidation activities in liver microsomes using liquid chromatography-tandem mass spectrometry. Anal Biochem. 2012;427:52-9 pubmed publisher..The method consists of incubations of probe substrates for UGT1A1 (etoposide), UGT1A3 (chenodeoxycholic acid), UGT1A4 (trifluoperazine), UGT1A6 (serotonin), UGT1A9 (mefenamic acid), and UGT2B7 (azidothymidine) with HLMs...
- Lopez M, Dorado P, Ortega A, Peñas Lledó E, Monroy N, Silva Zolezzi I, et al. Interethnic differences in UGT1A4 genetic polymorphisms between Mexican Mestizo and Spanish populations. Mol Biol Rep. 2013;40:3187-92 pubmed publisherUDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs...
- Kimura Y, Shibata M, Tamada M, Ozaki N, Arai K. Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis. In Vivo. 2017;31:811-817 pubmed..In contrast, the analgesic effect of morphine increased 4-fold in AA rats. Our results showed that the pharmacokinetics of morphine is not changed, but the pharmacodynamics of morphine is enhanced in chronic inflammation. ..
- Hong X, Zheng Y, Qin Z, Wu B, Dai Y, Gao H, et al. In Vitro Glucuronidation of Wushanicaritin by Liver Microsomes, Intestine Microsomes and Expressed Human UDP-Glucuronosyltransferase Enzymes. Int J Mol Sci. 2017;18: pubmed publisher..Taken together, UGT1A1, 1A3, 1A7, 1A8, 1A9 and 2B7 were identified as the main UGT contributors responsible for wushanicaritin glucuronidation. ..
- Nakajima M, Tanaka E, Kwon J, Yokoi T. Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Drug Metab Dispos. 2002;30:1484-90 pubmed..and cotinine N-glucuronidations in the recombinant human UDP-glucuronosyltransferases (UGTs) (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15) expressed in baculovirus-infected insect cells or ..