Zhu_2003_Biochim.Biophys.Acta_1638_208

Reference

Title : Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia - Zhu_2003_Biochim.Biophys.Acta_1638_208
Author(s) : Zhu QS , Xing W , Qian B , von Dippe P , Shneider BL , Fox VL , Levy D
Ref : Biochimica & Biophysica Acta , 1638 :208 , 2003
Abstract :

Microsomal epoxide hydrolase (mEH) is a bifunctional protein that plays a central role in carcinogen metabolism and is also able to mediate the sodium-dependent uptake of bile acids into hepatocytes. Studies have identified a subject (S-1) with extremely elevated serum bile salt levels in the absence of observable hepatocellular injury, suggesting a defect in bile acid uptake. In this individual, mEH protein and mEH mRNA levels were reduced by approximately 95% and 85%, respectively, whereas the expression and amino acid sequence of another bile acid transport protein (NTCP) was unaffected. Sequence analysis of the mEH gene (EPHX1) revealed a point mutation at an upstream HNF-3 site (allele I) and in intron 1 (allele II), which resulted in a significant decrease in EPHX1 promoter activity in transient transfection assays. Gel shift assays using a radiolabeled oligonucleotide from each region resulted in specific transcription factor binding patterns, which were altered in the presence of the mutation. These studies demonstrate that the expression of mEH is greatly reduced in a patient with hypercholanemia, suggesting that mEH participates in sodium-dependent bile acid uptake in human liver where its absence may contribute to the etiology of this disease.

PubMedSearch : Zhu_2003_Biochim.Biophys.Acta_1638_208
PubMedID: 12878321
Gene_locus related to this paper: human-EPHX1

Related information

Citations formats

Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D (2003)
Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia
Biochimica & Biophysica Acta 1638 :208

Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D (2003)
Biochimica & Biophysica Acta 1638 :208