Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

2016 ◽  
Vol 201 (4) ◽  
pp. 277-286 ◽  
Author(s):  
Katerina Cizkova ◽  
Aneta Rajdova ◽  
Jiri Ehrmann
Keyword(s):  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Prenatal Development ◽  
Intrauterine Development ◽  
Highly Active ◽  
Key Factor ◽  
Liver And Kidney ◽  
Spatio Temporal ◽  
Human Prenatal Development ◽  
Temporal Expression Pattern

Soluble epoxide hydrolase (sEH) converts highly active epoxyeicosatrienoic acids (EETs) generated by cytochrome P450 (CYP) epoxygenases from arachidonic acid to less active dihydroxyeicosatrienoic acids. Because of the role of EETs in processes potentially relevant to the development of organisms, EETs could be suggested as potential morphogens. Unfortunately, only little is known about sEH expression during human intrauterine development (IUD). We investigated the spatio-temporal expression pattern of sEH in human embryonic/foetal intestines, liver and kidney from the 6th to the 20th week of IUD by two-step immunohistochemistry. sEH was expressed during the whole tested period of prenatal development and its level of expression remained more or less the same during the estimated period of IUD. Distribution of CYP epoxygenases and sEH in the intestinal epithelium and the nephrogenic zone of the kidney suggests an influence of EETs on cell proliferation and differentiation and, consequently, on the development of intestines and kidney. Thus, alterations in the strict spatio-temporal pattern of expression of CYP epoxygenases and/or sEH during human prenatal development by xenobiotics could have a harmful impact for developing organisms.

Soluble Epoxide Hydrolase as an Important Player in Intestinal Cell Differentiation

2020 ◽  
Vol 209 (4-6) ◽  
pp. 177-188
Author(s):  
Katerina Cizkova ◽  
Katerina Koubova ◽  
Tereza Foltynkova ◽  
Jana Jiravova ◽  
Zdenek Tauber
Keyword(s):  
Cell Differentiation ◽  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Intestinal Cell ◽  
Caco2 Cells ◽  
Important Player ◽  
Ht 29

There is growing evidence that soluble epoxide hydrolase (sEH) may play a role in cell differentiation. sEH metabolizes biologically highly active and generally cytoprotective epoxyeicosatrienoic acids (EETs), generated from arachidonic acid metabolism by CYP epoxygenases (CYP2C and CYP2J subfamilies), to less active corresponding diols. We investigated the effect of sEH inhibitor (TPPU) on the expression of villin, CYP2C8, CYP2C9, CYP2J2, and sEH in undifferentiated and in vitro differentiated HT-29 and Caco2 cell lines. The administration of 10 μM TPPU on differentiated HT-29 and Caco2 cells resulted in a significant decrease in expression of villin, a marker for intestinal cell differentiation. It was accompanied by a disruption of the brush border when microvilli appeared sparse and short in atomic force microscope scans of HT-29 cells. Although inhibition of sEH in differentiated HT-29 and Caco2 cells led to an increase in sEH expression in both cell lines, this treatment had an opposite effect on CYP2J2 expression in HT-29 and Caco2 cells. In addition, tissue samples of colorectal carcinoma and adjacent normal tissues from 45 patients were immunostained for sEH and villin. We detected a significant decrease in the expression of both proteins in colorectal carcinoma in comparison to adjacent normal tissue, and the decrease in both sEH and villin expression revealed a moderate positive association. Taken together, our results showed that sEH is an important player in intestinal cell differentiation.

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