Glucuronidation Activity of the UGT2B17 Enzyme toward Xenobiotics

Turgeon, David; Carrier, Jean-Sébastien; Chouinard, Sarah; Bélanger, Alain

doi:10.1124/dmd.31.5.670

Cited by 88 publications

(76 citation statements)

References 28 publications

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“…UGT2B15 is abundantly detected in the liver, and also detected in the stomach, breast, small intestine, and colon, as well as prostate in relatively large amounts. UGT2B15 has been fully characterized for its ability to conjugate with drugs, environmental pollutants, and dietary components (Green et al, 1994) and shares more than 95% homology with UGT2B17, which is one of the most important conjugate enzymes in androgen metabolism (Turgeon et al, 2003).…”

Section: Results Of Quantitative Determination For the Ugt1a Subfamilymentioning

confidence: 99%

Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction

Ohno¹,

Nakajin²

2008

Drug Metab Dispos

383

400

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ABSTRACT:An exhaustive real-time reverse transcriptase-polymerase chain reaction (PCR) quantification method was used to determine 15 of the catalytically active human UDP-glucuronosyltransferase (UGT) isoforms (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, and 2B17). The specific primers for respective human UGTs were developed for differential determination. The cDNA derived from the 1A7 isoform was detected in the esophagus, the 1A8 and 1A10 isoforms were detected in the small intestine, and all other isoforms were detected in at least the liver by PCR. In all cases, single bands of the expected size on the agarose gel were confirmed to correspond with the predicted UGT isoform sequences. Each calibration curve showed linearity between the PCR crossing point and the calibrator copy number. The correlation coefficients were greater than 0.9957 with high reproducibility. This exhaustive measurement method was applied to UGT expression in 23 human tissue types. UGT was mostly expressed in the alimentary system and liver. We were surprised to find that extremely high expression in the liver was found for UGT2B4 and UGT2B15, which had, respectively, 8.98 and 4.38 times greater expression than UGT2B7 in the liver. In addition, even though expressed at low levels, several UGT isoforms were expressed in steroidogenic tissues, such as the breast, prostate, heart, and adrenal. Therefore, this quantification method may provide valuable information about the medical efficacy or pharmacokinetic characteristics of a wide variety of UGT-metabolized drugs.

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Section: Results Of Quantitative Determination For the Ugt1a Subfamilymentioning

confidence: 99%

Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction

Ohno¹,

Nakajin²

2008

Drug Metab Dispos

383

400

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“…UGT2B17 is a member of the uridine diphosphoglucuronosyltransferase (UGT) protein family and catalyzes the glucuronidation of a diverse range of substrates including steroid hormones and lipid-soluble drugs. 4,5 Therapies commonly used in CLL such as those in the FC regimen are not known to be influenced by UGT2B17. Gruber and colleagues preliminarily tried to explore how UGT2B17 For personal use only.…”

Section: Ugt2b17 As a Disease Accelerator In Cllmentioning

confidence: 99%

“…Current data from experimental systems indicate that lentiviruses have significantly lower genotoxicity compared with the long terminal repeat-driven ␥-retroviral retroviruses used in earlier trials of gene therapy in other immunodeficiencies that resulted in cases of leukemogenesis directly linked to the therapy: X-linked severe combined immunodeficiency (SCID), 3 Wiskott Aldrich syndrome, 4 and X-linked chronic granulomatous disease. 5,6 In addition to selection of the safest effective vector, the time frame and intensity of patient conditioning after stem cell harvest but before infusion of gene-corrected autologous stem cells requires thoughtful planning and discussion.…”

mentioning

confidence: 99%

UGT2B17 as a disease accelerator in CLL

Zhong

Byrd

2013

Blood

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“…UGT2B17 is a family 2B UGT that glucuronidates xenobiotics, carcinogens, and C 19 steroids (27,28). UGT2B17 is expressed in liver and multiple extrahepatic tissues including the lung (27).…”

Section: Introductionmentioning

confidence: 99%

The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer

Gallagher¹,

Muscat²,

Hicks³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in f10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro. In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes (P = 0.058).There were no significant differences in this ratio by genotype in men (P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3). The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer Epidemiol Biomarkers Prev 2007;16(4):823 -8)

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Glucuronidation Activity of the UGT2B17 Enzyme toward Xenobiotics

Cited by 88 publications

References 28 publications

Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction

Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction

UGT2B17 as a disease accelerator in CLL

The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer

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