High impact information on UGT2B@

• Thus, tissue-specific and interindividual polymorphic regulation of UGT1A and UGT2B genes in small intestine is identified and implicated as molecular biological determinant contributing to interindividual prehepatic drug and xenobiotic metabolism in humans [1].
• To isolate cDNA clones encoding novel UGT2B enzymes, human prostate and LNCaP cell cDNA libraries were screened using a pool of steroid-specific UGT2B cDNA probes [2].
• The tissue distribution and cellular localization of the UGT2B transcripts and proteins in humans clearly indicate that these enzymes are synthesized in androgen-sensitive tissues [3].
• To determine whether this putative Pbx site contributes to the regulation of UGT2B expression, we chose the UGT2B17 gene and investigated the capacity of its Pbx site to bind specific transcription factors and alter promoter activity [4].
• In some of these UGT2B genes, a putative pre-B cell homeobox (Pbx) transcription factor binding site is found directly adjacent to the functional HNF1 site [4].

Biological context of UGT2B@

• Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13 [5].
• A yeast artificial chromosome contig containing the UGT2B4, UGT2B9, and UGT2B15 genes was isolated, and pulsed-field gel electrophoresis and PCR revealed that several members of the human UGT2B gene subfamily are clustered within a 195-kb region of the YAC contig [5].
• A novel UGT2B cDNA clone UGT2B4(E458) was isolated from human prostate and LNCaP cell cDNA libraries [6].
• This paper describes the genomic characterization and chromosomal localization of three UGT2B genes which together comprise part of a large cluster of related sequences, including pseudogenes found on human chromosome 4q13 [7].
• Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members [8].

Anatomical context of UGT2B@

• Here we report the mapping of two additional human UGT2B genes to chromosome 4 utilizing the polymerase chain reaction (PCR) and a panel of human/rodent somatic cell hybrid cell lines [5].
• The results showed that UGT2B isoforms mainly contribute to AS-3201 N-glucosidation in human liver microsomes [9].
• In addition, the activity of AS-3201 N-glucosyltransferase significantly correlated with that of amobarbital N-glucosyltransferase in microsomes from sixteen human livers (r=0.964, P<0.01), indicating that UGT2B isoforms were also involved in the barbiturate N-glucosidation in humans [9].
• UGT2B RNA expression was examined in mucosa from stomach to colon from two subjects [10].
• Immunohistochemical studies performed in monkey kidney cortex reveal a restrictive expression of UGT2B proteins in the epithelial cells of the proximal tubules [11].

Associations of UGT2B@ with chemical compounds

• In summary, our data showed that several members of UGT1A and UGT2B families are capable of converting LA and AA metabolites into glucuronide derivatives, which is considered an irreversible step to inactivation and elimination of endogenous substances from the body [12].
• Treatment of stable cells with actinomycin D reveals that UGT2B transcripts are stable for 12 h, except for the UGT2B4 transcript, which was decreased by 50% after the 12-h incubation period [8].
• Cycloheximide treatment of stably transfected HK293 cells demonstrated that the UGT2B17 protein is more labile than the other enzymes; the protein levels decrease after 1 h of treatment, whereas other UGT2B proteins were stable for at least 12 h [8].
• The findings of this study clearly show that UGT2B specifically utilizes UDP-glucose but not UDP-glucuronic acid as a sugar donor for the conjugation of AS-3201 in human liver microsomes [9].
• Measurement of aldosterone glucuronidation and normalization with the UGT2B protein contents in monkey tissues demonstrate that liver and kidney glucuronidate this hormone with a similar velocity [11].

Other interactions of UGT2B@

• Localization of a bile acid UDP-glucuronosyltransferase gene (UGT2B) to chromosome 4 using the polymerase chain reaction [13].
• UGT2B7 was the only product of the UGT2 gene family examined and it metabolized all the aromatic amines at similar low relative levels compared with a preferred substrate, 4-OH-estrone [14].
• The deduced amino acid sequences of UGTs 2B10 and 2B11 share > 76% sequence similarity with other known human liver UGT2B subfamily isoforms and < 48% sequence similarity with UGT1 family proteins [15].
• Treatment with both DHT (0.5 nM) and EGF (10 ng/ml) caused a greater decrease of DHT glucuronidation and UGT2B messenger RNA levels than when the cells were treated with either compound alone [16].
• The gastrointestinal tract, contains several UDP-glucuronosyltransferases (UGTs) of the UGT1A and UGT2B subfamilies [17].

Analytical, diagnostic and therapeutic context of UGT2B@

• Western blot analysis of the UGT2B18-HK293 cell line using a human UGT2B17 polyclonal antibody (EL-93) revealed high expression of a 53 kDa UGT2B protein [18].
• Northern blot analysis also demonstrated a decrease in the steady-state level of UGT2B transcripts [16].
• The sites of placental UGT2B transcription (in situ hybridization) and protein expression (immunohistochemistry) were located in the syncytium of the placental trophoblasts bordering the placental villi [19].
• Although it is widely recognized that the liver is a major site of steroid glucuronidation, RT-PCR analysis has shown the expression of UGT2B transcripts in extrahepatic steroid target tissues such as the prostate [20].
• To investigate the cellular localization of UGT2B expression in the human prostate, the present in situ hybridization studies demonstrated the presence of UGT2B transcripts in epithelial cells lining the acinii [20].

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