UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term

Collier, Abby C.; Ganley, Natalie A.; Tingle, Malcolm D.; Blumenstein, Marion; Marvin, Keith W.; Paxton, James W.; Mitchell, Murray D.; Keelan, Jeffrey A.

doi:10.1016/s0006-2952(01)00890-5

Cited by 96 publications

(56 citation statements)

References 41 publications

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“…Kaivosaari et al (2007) reported that UGT1A4 was detected in trachea, kidney, small intestine, and colon at comparatively low levels relative to those in the liver using realtime PCR, whereas we only detected it in liver. Moreover, Collier et al (2002) reported that most UGT2B isoforms were expressed in human placenta using RT-PCR, whereas we detected only UGT1A5 in the placenta. The discrepancy in these results may be due to 1) the high interindividual variability in UGT isoform expression levels and thus the necessity for an exhaustive quantitative determination method and 2) configuration of a slightly lower amplification efficiency with use of the quantification primer set, such as UGT2B10, UGT2B11, and UGT2B15 (Fig.…”

Section: Results Of Quantitative Determination For the Ugt1a Subfamilymentioning

confidence: 58%

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

380

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: 58%

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

380

400

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“…Mice may have a similar mechanism of controlling Ugt1a6 expression, as noted above for rats, based on its ubiquitous expression profile and the predicted alternative start site sequences (www.ensembl.org). In human placenta, six UGT2B members were expressed; however, in this study, only Ugt2b35 was barely detectable in mouse placenta, implicating differences in placental biotransformation between species (Collier et al, 2002). RNA from other steroid-sensitive tissues was not analyzed in this study, leaving in question the expression of UGTs in such tissues.…”

Section: Downloaded Frommentioning

confidence: 66%

Tissue- and Gender-Specific mRNA Expression of UDP-Glucuronosyltransferases (UGTs) in Mice

2006

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ABSTRACT:UDP-glucuronosyltransferases (UGTs) catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. Currently, little information regarding tissue-or genderspecific expression of mouse UGTs is available. Mice are increasingly popular models in biomedical research, and therefore, thorough characterization of murine drug metabolism is desired. The purpose of the present study was to determine both tissueand gender-specific UGT gene expression profiles in mice. RNA from 14 tissues was isolated from male and female C57BL/6 mice and UGT expression was determined by the branched DNA signal amplification assay. UGTs highly expressed in mouse liver include Ugt1a1, Ugt1a5, Ugt1a6, Ugt1a9, Ugt2a3, Ugt2b1, Ugt2b5/37/38, Ugt2b34, Ugt2b35, and Ugt2b36. Several isoforms were expressed in the gastrointestinal (GI) tract, including Ugt1a6, Ugt1a7c, Ugt2a3, Ugt2b34, and Ugt2b35. In kidney, Ugt1a2, Ugt1a7c, Ugt2b5/37/38, Ugt2b35, and Ugt3a1/2 were expressed. UGT expression was also observed in other tissues: lung (Ugt1a6), brain (Ugt2b35), testis and ovary (Ugt1a6 and Ugt2b35), and nasal epithelia (Ugt2a1/2). Male-predominant expression was observed for Ugt2b1 in liver, Ugt2b5/37/38 in kidney, and Ugt1a6 in lung. Female-predominant expression was observed for Ugt1a1 and Ugt1a5 in liver, Ugt1a2 in kidney, Ugt2b35 in brain, and Ugt2a1/2 in nasal epithelia. UDP-glucose pyrophosphorylase was highly expressed in liver, kidney, and GI tract, whereas UDP-glucose dehydrogenase was highly expressed in the GI tract. In conclusion, marked differences in tissue-and gender-specific expression patterns of UGTs exist in mice, potentially influencing drug metabolism and pharmacokinetics.

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“…The UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 belong among the main liver xenobiotic-conjugating enzymes, whereas UGT1A7, UGT1A8, and UGT1A10 are predominantly extrahepatic UGT forms. Moreover, glucuronidation activity was also detected in other tissues such as kidney (Sutherland et al, 1993), brain (King et al,1999), or placenta (Collier et al, 2002).…”

Section: Human Forms Of Ugts and Their Tissue Distributionmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term

Cited by 96 publications

References 41 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

Tissue- and Gender-Specific mRNA Expression of UDP-Glucuronosyltransferases (UGTs) in Mice

Phase II Drug Metabolism

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