Cell surface expression and bile acid transport function of one topological form of m-epoxide hydrolase

Dippe, P von; Zhu, Qin-shi; Lévy, Daniel

doi:10.1016/j.bbrc.2003.08.074

Cited by 19 publications

(18 citation statements)

References 23 publications

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“…Inside the cells, their epitope expression profile was basically similar to that of the primary hepatocytes. The absence of surface expression of mEH was in accordance with the finding that rat hepatocytes lose their expression of mEH on the surface in 72 h of culture (von Dippe et al , 2003). HCC lines Huh-7 and HepG2 displayed significant levels of mEH expression on the surface, and the pattern of the expression of the five epitopes was similar to that of primary hepatocytes.…”

Section: Discussionsupporting

confidence: 88%

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

Duan

Takagi

Kayano

et al. 2012

Toxicology and Applied Pharmacology

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In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside of both cell types, but most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines were also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells.

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Section: Discussionsupporting

confidence: 88%

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

Duan

Takagi

Kayano

et al. 2012

Toxicology and Applied Pharmacology

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“…Although transfection of mEH cDNA into MDCK cells resulted in expression of Na + -dependent bile acid transport in one study (181), another study failed to show Na + -dependent bile acid transport in a fibroblast cell line stably transfected with mEH cDNA or in hepatoma cell lines that express mEH (75). In response to these negative studies, it was suggested that mEH is only intracellular and not targeted to the plasma membrane in these cells (186). As of the present time, the potential role of mEH in bile acid transport remains an open question.…”

Section: Transport Of Bile Acidsmentioning

confidence: 99%

Organic Anion Uptake by Hepatocytes

Wolkoff

2014

Comprehensive Physiology

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Many of the compounds taken up by the liver are organic anions that circulate tightly bound to protein carriers such as albumin. The fenestrated sinusoidal endothelium of the liver permits these compounds to have access to hepatocytes. Studies to characterize hepatic uptake of organic anions through kinetic analyses, suggested that it was carrier-mediated. Attempts to identify specific transporters by biochemical approaches were largely unsuccessful and were replaced by studies that utilized expression cloning. These studies led to identification of the organic anion transport proteins (oatps), a family of 12 transmembrane domain glycoproteins that have broad and often overlapping substrate specificities. The oatps mediate Na+-independent organic anion uptake. Other studies identified a seven transmembrane domain glycoprotein, Na+/taurocholate transporting protein (ntcp) as mediating Na+-dependent uptake of bile acids as well as other organic anions. Although mutations or deficiencies of specific members of the oatp family have been associated with transport abnormalities, there have been no such reports for ntcp, and its physiologic role remains to be determined, although expression of ntcp in vitro recapitulates the characteristics of Na+-dependent bile acid transport that is seen in vivo. Both ntcp and oatps traffic between the cell surface and intracellular vesicular pools. These vesicles move through the cell on microtubules, using the microtubule based motors dynein and kinesins. Factors that regulate this motility are under study and may provide a unique mechanism that can alter the plasma membrane content of these transporters and consequently their accessibility to circulating ligands.

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“…The protein is attached to the cytosolic site of the endoplasmic reticulum membrane with its N-terminal membrane anchor (Friedberg et al 1994a;Holler et al 1997), which correlates to the membrane topology of CYPs. Some reports though claim a localisation of mEH in the plasma membrane, based on the enzymes possible function in bile acid transport (Zou et al 2000;von Dippe et al 2003) which is, however, a matter for debate (Honscha et al 1995).…”

Section: Organ and Cellular Distributionmentioning

confidence: 99%

Mammalian epoxide hydrolases in xenobiotic metabolism and signalling

2009

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Epoxide hydrolases catalyse the hydrolysis of electrophilic-and therefore potentially genotoxic-epoxides to the corresponding less reactive vicinal diols, which explains the classiWcation of epoxide hydrolases as typical detoxifying enzymes. The best example is mammalian microsomal epoxide hydrolase (mEH)-an enzyme prone to detoxiWcation-due to a high expression level in the liver, a broad substrate selectivity, as well as inducibility by foreign compounds. The mEH is capable of inactivating a large number of structurally diVerent, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse eVects of foreign compounds. Furthermore, evidence is accumulating that mammalian epoxide hydrolases play physiological roles other than detoxiWcation, particularly through involvement in signalling processes. This certainly holds true for soluble epoxide hydrolase (sEH) whose main function seems to be the turnover of lipid derived epoxides, which are signalling lipids with diverse functions in regulatory processes, such as control of blood pressure, inXammatory processes, cell proliferation and nociception. In recent years, the sEH has attracted attention as a promising target for pharmacological inhibition to treat hypertension and possibly other diseases. Recently, new hitherto uncharacterised epoxide hydrolases could be identiWed in mammals by genome analysis. The expression pattern and substrate selectivity of these new epoxide hydrolases suggests their participation in signalling processes rather than a role in detoxiWcation. Taken together, epoxide hydrolases (1) play a central role in the detoxiWcation of genotoxic epoxides and (2) have an important function in the regulation of physiological processes by the control of signalling molecules with an epoxide structure.

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Cell surface expression and bile acid transport function of one topological form of m-epoxide hydrolase

Cited by 19 publications

References 23 publications

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

Organic Anion Uptake by Hepatocytes

Mammalian epoxide hydrolases in xenobiotic metabolism and signalling

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