Characterization and tissue specificity of a monoclonal antibody against human uridine 5′-diphosphate-glucuronosyltransferase

Peters, Wilbert H.M.; Allebes, Wil A.; Jansen, Petér L. M.; Poels, L. G.; Capel, P. J. A.

doi:10.1016/0016-5085(87)90329-5

Cited by 66 publications

(37 citation statements)

References 17 publications

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“…In both cases, the crypt cell activities were induced to the greatest extent (Dubey and Singh, 1988). Similarly, the highest concentrations of UGTs in the human small intestine were detected in the villous tips (Peters et al, 1987). The major UGT1 form induced by 2-naphthoflavone in the rat small intestine is UGT1A7 (Kobayashi et al, 1998).…”

Section: Udp-glucuronosyltransferasesmentioning

confidence: 94%

The Small Intestine as a Xenobiotic-Metabolizing Organ

Kaminsky

Zhang²

2003

Drug Metab Dispos

202

149

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Section: Udp-glucuronosyltransferasesmentioning

confidence: 94%

The Small Intestine as a Xenobiotic-Metabolizing Organ

Kaminsky

Zhang²

2003

Drug Metab Dispos

202

149

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“…The UGT1A1 antibody WP1 served as a positive control. 37 Antibodies were detected with anti mouse peroxidase (Biorad) or anti-rat peroxidase (Nordic) and ECL chemiluminescence reagent (Amersham-Pharmacia). Images were recorded using a lumi imager (Roche).…”

Section: Western Blottingmentioning

confidence: 99%

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Seppen¹,

Til²,

Rijt³

et al. 2005

Gene Ther

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Gene therapy for inherited disorders might cause an immune response to the therapeutic protein. A solution would be to introduce the gene in the fetal or neonatal period, which should lead to tolerization. Lentiviral vectors mediate long-term gene expression, and are well suited for gene therapy early in development. A model for fetal or neonatal gene therapy is the inherited disorder of bilirubin metabolism, Crigler-Najjar disease (CN). The absence of bilirubin UDP-glucoronyltransferase (UGT1A1) activity in CN patients causes high serum levels of unconjugated bilirubin and brain damage in infancy. CN is attractive for the development of gene therapy because the mutant Gunn rat closely mimics the human disease.Injection of UGT1A1 lentiviral vectors corrected the hyperbilirubinemia for more than a year in rats injected as fetuses and for up to 18 weeks in rats injected the day of birth. UGT1A1 gene transfer was confirmed by the presence of bilirubin glucuronides in bile. All animals injected with UGT1A1 lentiviral vectors developed antibodies to UGT1A1. Animals injected with green fluorescent protein (GFP) lentiviral vectors did not develop antibodies to GFP. Our results indicate that fetal and neonatal gene therapy with immunogenic proteins such as UGT1A1 does not necessarily lead to tolerization.

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“…Western blotting was performed with the monoclonal antibody WP1 [23], which recognizes human B-UGT. In homogenates of COS-7 cells transfeeted with wild type B-UGT (lane marked wt), a 51 kDa protein is detected, in homogenates of COS-7 cells transfected with 15-Arg/B-UGT (lane marked mut), no B-UGT could be detected (Fig.…”

Section: Expression Of Wild Type and 15-arg/b-ugt In Cos-7 Cellsmentioning

confidence: 99%

A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP‐glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler‐Najjar type IIs

et al. 1996

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Crigler-Najjar (CN) disease is caused by a deficiency of the hepatic enzyme, bilirubin UDP-glucuronosyltransferase (B-UGT). We have found two CN type II patients, who were homozygous for a leucine to arginine transition at position 15 of B-UGT1. This mutation is expected to disrupt the hydrophobic core of the signal peptide of B-UGT1. Wild type and mutant B-UGT cDNAs were transfected in COS cells. Mutant and wild type mRNA were formed in equal amounts. The mutant protein was expressed with 0.5% efficiency, as compared to wild type. Mutant and wild type mRNAs were translated in vitro. Wild type transferase is processed by microsomes, no processing of the mutant protein was observed.

show abstract

Characterization and tissue specificity of a monoclonal antibody against human uridine 5′-diphosphate-glucuronosyltransferase

Cited by 66 publications

References 17 publications

The Small Intestine as a Xenobiotic-Metabolizing Organ

The Small Intestine as a Xenobiotic-Metabolizing Organ

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP‐glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler‐Najjar type IIs

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