Coimmunoprecipitation was used to investigate protein-protein interactions between several UDP-glucuronosyltransferase (UGT) isoforms and cytochrome P450 3A4. Solubilized human liver microsomes were incubated with specific antibodies to UGT2B7, UGT1A6, UGT1A1, and CYP3A4, and the immunoprecipitates were run on SDS-polyacrylamide gel electrophoresis. Western blots showed that UGT2B7, UGT1A6, UGT...

The major enzyme responsible for the glucuronidation of bilirubin is the uridine 5'-diphosphoglucose glucuronosyltransferase A1 (UGT1A1) enzyme, and genetic variation in the UGT1A1 gene is reported to influence the bilirubin concentration in the blood. In this study, we have investigated which gene-/haplotype variants may be useful for genetic testing of Gilbert's syndrome. Two groups of sample...

Humanized mice that express the human UDP-glucuronosyltransferase (UGT) 1 locus have been developed in a Ugt1-null background as a model to improve predictions of human UGT1A-dependent drug clearance. Enzyme kinetic parameters (K(m) and V(max)) and pharmacokinetic properties of three probe drugs were compared using wild-type and humanized UGT1 mice that express the Gilbert's UGT1A1*28 allele [T...

Hodgkin lymphoma is a highly curable malignancy, but treatment outcome might be influenced by inherited gene polymorphisms determining anticancer agent metabolism. We prospectively collected peripheral blood lymphocytes from 313 patients with Hodgkin lymphomas to analyze GSTP1, GSTM1, GSTT1, UGT1A1, and CYP3A4 enzyme gene polymorphisms. All patients were treated with chemotherapy, associated wi...

Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme--UDP-glucuronosyltransferase (UGT) 1A1--to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) m...

BACKGROUND The UGT1A1 gene encodes a responsible enzyme, UDP-glucuronosyltransferase1A1 (UGT1A1), for bilirubin metabolism. Many mutations have already been identified in patients with inherited disorders with unconjugated hyperbilirubinemia, such as Crigler-Najjar syndromes and Gilbert's syndrome. CASE PRESENTATION In this report, we presented a boy with intermittent unconjugated hyperbiliru...

To the Editor: Recent progress in human genome analysis has been providing tools for a new approach to disease treatment based on individual differences identified by use of genetic information. The feasibility of genotyping for DNA polymorphisms before treatment depends on the availability of rapid, accurate, and efficient geno-typing methods. We previously reported that genetic polymorphisms ...

11 Background: The UGT1A1 gene encodes a responsible enzyme, 12 UDP-glucuronosyltransferase1A1 (UGT1A1), for bilirubin metabolism. Many 13 mutations have already been identified in patients with inherited disorders with 14 unconjugated hyperbilirubinemia, such as Crigler-Najjar syndromes and Gilbert’s 15 syndrome. 16 Case presentation: In this report, we presented a boy with intermittent 17 unc...

The co-ordinated induction of several hepatic drug-metabolizing enzymes is a common feature in the regulation of drug biotransformation under normal and pathological conditions. In the present study the activity and expression of bilirubin UDP-glucuronosyltransferase (UGT1A1) were investigated in livers of BioBreeding/Worcester diabetic, fasted and acetone-treated rats. Bilirubin glucuronidatio...

Many phase I and II enzymes are under hormonal regulation, resulting in sex-related expression patterns. This sex-related enzyme expression can result in differential metabolism of physiologically active endogenous substances, altered xenobiotic clearance, and differences in susceptibility to drug toxicities. Treatment of female Sprague-Dawley (SD) rats with 5 mg testosterone propionate/kg/day,...