Disease relevance of LOC286989

• Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of crigler-najjar syndrome type I with a chimeric oligonucleotide [1].
• Whereas saquinavir also competitively inhibits UGT activity, this drug has not been associated with hyperbilirubinemia, most likely because of the higher K(I) (360 microM) and substantially lower therapeutic levels as compared with indinavir [2].
• Increased UDP-glucuronosyltransferase in rat hepatocyte nodules and hepatocellular carcinomas produced by feeding 2-acetylaminofluorene or N-nitrosomorpholine was studied using isozyme-selective substrates, antibodies, and DNA probes [3].
• Function and regulation of UDP-glucuronosyltransferase genes in health and liver disease: report of the Seventh International Workshop on Glucuronidation, September 1993, Pitlochry, Scotland [4].
• Crigler-Najjar (CN) patients have no bilirubin UDP glucuronosyltransferase (UGT1A1) activity and suffer brain damage because of bilirubin toxicity [5].

High impact information on LOC286989

• Indinavir was found to competitively inhibit UGT enzymatic activity (K(I) = 183 microM) while concomitantly inducing hepatic bilirubin UGT mRNA and protein expression [2].
• The glucuronidation of testosterone, androsterone, and estrone was not catalyzed by this cloned UDP-glucuronosyltransferase [6].
• The purified IgG was used for immunocytochemical localization of UDP-glucuronosyltransferase in rat liver, jejunum, kidney, and adrenal gland [7].
• In addition, mRNA levels for ST2A2, a female-specific ST gene, were suppressed 50% in females and induced 120% over control in males. mRNA expression for all other forms of rat liver UGT and ST isozymes that were tested was not significantly affected by tamoxifen treatment [8].
• Potential genoprotective role for UDP-glucuronosyltransferases in chemical carcinogenesis: initiation of micronuclei by benzo(a)pyrene and benzo(e)pyrene in UDP-glucuronosyltransferase-deficient cultured rat skin fibroblasts [9].

Chemical compound and disease context of LOC286989

• The Gunn rat is a mutant strain of Wistar rat which has unconjugated hyperbilirubinemia as a result of the absence of hepatic UDP-glucuronosyltransferase (UDPGT) activity toward bilirubin [10].
• In the rat, UDP-glucuronosyltransferase activities towards bilirubin, morphine and testosterone increase markedly after normal or premature birth [11].
• The novel bilirubin/phenol UDP-glucuronosyltransferase UGT1 gene locus: implications for multiple nonhemolytic familial hyperbilirubinemia phenotypes [12].
• As a result of liver hypertrophy, the active rats showed higher total liver activity of several biotransformation enzymes, including 2-naphthol sulfotransferase, styrene oxide hydrolase, benzphetamine N-demethylase, ethacrynic acid glutathione S-transferase and morphine UDP-glucuronosyltransferase (P less than 0.05) [13].
• In contrast, the addition of UDP glucuronate (10 mM) in the presence of the UDP-glucuronosyltransferase activator UDP-N-acetylglucosamine (10 mM) had little effect on cyclophosphamide toxicity [14].

Biological context of LOC286989

• We have isolated genomic DNA clones containing rat UDP-glucuronosyltransferase family 1 (UGT1) sequences and have shown drug-responsive and tissue-specific alternative expression of multiple first exons (Emi, Y., Ikushiro, S., and Iyanagi, T. (1995) J. Biochem. (Tokyo) 117, 392-399) [15].
• Xenobiotic responsive element-mediated transcriptional activation in the UDP-glucuronosyltransferase family 1 gene complex [15].
• The predicted amino acid sequence of LC14 is nearly identical (5 differences out of 531 residues) to that deduced from UGT1A7, recently cloned at the genomic DNA level (Emi, Y., Ikushiro, S., and Kyanagi, T. (1995) J. Biochem. (Tokyo) 117, 392-399) [16].
• Nucleotide sequence determination revealed that bilirubin- and 3-MC-inducible UDPGT mRNAs in Gunn rats contain an identical frame-shift deletion of a single guanosine residue within the common region of their coding sequences [17].
• The 3-methylcholanthrene-inducible UDP-glucuronosyltransferase deficiency in the hyperbilirubinemic rat (Gunn rat) is caused by a -1 frameshift mutation [18].

Anatomical context of LOC286989

• BHT and BHA increased UDP-glucuronosyltransferase activities in liver microsomes for p-nitrophenol (236 and 218%, respectively), 3-hydroxybenzo(a)pyrene (246 and 175%, respectively), and androsterone (269 and 152%, respectively) [19].
• In addition to inducing hepatic enzyme activities, BHT and BHA increased the activity of UDP-glucuronosyltransferase in the small intestine and kidney [19].
• UDPGTr-3 and a related phenobarbital-inducible form of UDP-glucuronosyltransferase (designated UDPGTr-2) were both expressed in COS cells and their capacities to glucuronidate 13 commonly used substrates were analyzed [20].
• A UDP-glucuronosyltransferase (UDPGT) isoenzyme capable of morphine glucuronidation has been purified to apparent homogeneity and partially characterized from hepatic microsomes of female Wistar rats which have low 3 alpha-hydroxysteroid UDPGT [21].
• The transport of glucuronides synthesized in the luminal compartment of the endoplasmic reticulum by UDP-glucuronosyltransferase isoenzymes was studied in rat liver microsomal vesicles [22].

Associations of LOC286989 with chemical compounds

• We have isolated cDNA clones of the mRNA for rat UDP-glucuronosyltransferase that catalyzes the glucuronidation of 4-nitrophenol, by using synthetic oligonucleotides as hybridization probes [23].
• Rat liver UDP-glucuronosyltransferase. Identification of cDNAs encoding two enzymes which glucuronidate testosterone, dihydrotestosterone, and beta-estradiol [20].
• UDP-glucuronosyltransferase (transferase) clones were isolated from a cDNA bank constructed in pBR322 using transferase-enriched mRNA from the livers of phenobarbital-treated rats [24].
• Neither enzyme was active towards estrone, androsterone and substrates typical of 3-methylcholanthrene-inducible forms of UDP-glucuronosyltransferase [20].
• Previous work has shown that polycyclic aromatic hydrocarbons and oltipraz both induce an unidentified rat liver UDP-glucuronosyltransferase with activity toward benzo(a)pyrene-7, 8-diol, the proximate carcinogenic form of benzo(a)pyrene [16].

Regulatory relationships of LOC286989

• All treatments except 3,4-TBB induced NADPH-cytochrome P-450 reductase and aminopyrine-N-demethylase activities while all treatments except 2,4,5-HBB induced ethoxyresorufin-O-deethylase and UDP-glucuronosyltransferase activities [25].

Other interactions of LOC286989

• Several other common substrates of UDP-glucuronosyltransferase were not conjugated by the UDPGTr-4 enzyme [26].
• Organization of the rat UDP-glucuronosyltransferase, UDPGTr-2, gene and characterization of its promoter [27].
• A phenobarbital-inducible rat hepatic microsomal UDP-glucuronosyltransferase (UDPGT) that catalyzes the glucuronidation of 4-hydroxybiphenyl (4-HBP) has been purified to homogeneity [28].
• Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site [29].
• Evaluation of octamethylcyclotetrasiloxane (D4) as an inducer of rat hepatic microsomal cytochrome P450, UDP-glucuronosyltransferase, and epoxide hydrolase: a 28-day inhalation study [30].

Analytical, diagnostic and therapeutic context of LOC286989

• Northern blot analysis showed that the concentration of UDP-glucuronosyltransferase mRNA paralleled the concentration of enzyme proteins and their respective levels of enzyme activity [19].
• Similar changes in the level of the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections [31].
• Western blot analysis of positive colonies, using anti-rat liver UGT antibodies, revealed the presence of an immunoreactive polypeptide of the expected molecular mass of 52 kDa [32].
• Induction of UDP-glucuronosyltransferase activity in the Reuber H-4-II-E hepatoma cell culture [33].
• The Gunn rat, which is deficient in the UDP-glucuronosyltransferase for bilirubin, promptly excreted polar conjugates of the dimethyl ester of bilirubin in bile after intravenous infusion of this ester [34].

References