Time-dependent expression of cytochrome p450 epoxygenases during human prenatal development

Čížková, Kateřina; Konieczna, Anna; Erdösová, Běla; Ehrmann, Jiří

doi:10.4161/org.27911

Cited by 16 publications

(20 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, CYP2C8 mRNA was expressed in all fetal tissues studied (adrenal, kidney, liver, and lung tissue), whereas CYP2C9 mRNA was restricted to the liver (Johansson et al, 2014). Another study detected CYP2C8, CYP2C9, and CYP2C19 protein in fetal liver, intestine, and kidney (Cizkova et al, 2014). One explanation for the role of CYP2C8 in the fetus during early pregnancy may be a need for CYP2C8 to metabolize endogenous compounds such as retinoic acids and hence protect the fetus from retinoic acidinduced embryotoxicity (Johansson et al, 2014).…”

Section: Expressionmentioning

confidence: 93%

“…Hepatic CYP2C8 mRNA and protein are expressed early in the prenatal development and reaches adult levels already in early childhood (Treluyer et al, 1997;Blanco et al, 2000;Naraharisetti et al, 2010;Cizkova et al, 2014;Johansson et al, 2014). CYP2C8 seems to be the predominant CYP2C isoform in fetal livers (Hakkola et al, 1994;Nishimura et al, 2003; et al., 2014).…”

Section: Expressionmentioning

confidence: 99%

“…CYP2C8 protein has been detected in heart, hepatocytes, kidney, salivary ducts, small and large intestine, adrenal cortical cells, and tonsils (Läpple et al, 2003;Enayetallah et al, 2004;Delozier et al, 2007;Cizkova et al, 2014). The expression of CYP2C8 and other CYP enzymes has recently been reviewed by Shahabi et al (2014).…”

Section: Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

et al. 2015

View full text Add to dashboard Cite

Section: Expressionmentioning

confidence: 93%

Section: Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

et al. 2015

View full text Add to dashboard Cite

“…Therefore, we decided to examine the expression pattern of sEH in human embryonic/foetal intestines, liver and kidneys and compared it to the expression pattern of CYP epoxygenases in these same organs (we described this recently [Cizkova et al, 2014]). …”

mentioning

confidence: 99%

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

Čížková¹,

Rajdová²,

Ehrmann³

2016

Cells Tissues Organs

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…The hypothesis exists that their products of arachidonic acid metabolism, the epoxyeicosatrienoic acids (EETs), could be potential morphogens, but no study bringing evidence of this role of EETs is available. However, CYP epoxygenases are up-regulated by PPARa in human beings, and their spatio-temporal expression pattern in human embryonic/ foetal tissues has been described recently [16]. It has also been noted that changes in the expression of CYP2C induced by the environmental teratogen trichloroethylene lead to improper development of the chicken heart [17].…”

Section: Resultsmentioning

confidence: 99%

Spatio‐Temporal Expression of Peroxisome Proliferator‐Activated Receptor α During Human Prenatal Development

Čížková

Rajdová

Ehrmann

2014

Basic Clin Pharma Tox

Self Cite

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor a (PPARa) is a ligand-dependent transcription factor which is activated by various endogenous as well as exogenous compounds. It is involved in the regulation of a variety of biological processes, such as nutrient metabolism, energy homoeostasis, immunological response and xenobiotic metabolism. Little is known about its expression during human prenatal development. We examined the spatio-temporal expression pattern of PPARa in human embryonic/foetal intestines, liver and kidney from the 5th to 20th week of prenatal life by indirect two-step immunohistochemistry. PPARa expression can already be detected in the early stages of prenatal development; as early as the 7th week of intrauterine development (IUD) in the intestines, 5th week of IUD in the liver and 6th week of IUD in the kidney. We found agedependent changes in the PPARa expression pattern in the intestines and kidney. These events occur approximately at the commencement of function of these organs. In the intestines, we detected an obvious change of the PPARa expression pattern along the crypt-villous axis in the 11th week of IUD. In the kidney, the most apparent change was increased expression of PPARa in glomeruli in the 12th week of IUD. Moreover, in the liver, we detected a strong positivity in part of the developing blood elements. Information about the spatio-temporal expression pattern of PPARa could be the first step in evaluating the potential harmful impact of a wide range of environmental or pharmaceutical compounds which serve as PPARa ligands on the developing human organism.Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear receptor superfamily. PPARs consist of three members: peroxisome proliferator-activated receptor a (PPARa), PPARb/d and PPARc. The receptors are encoded by different genes and activated by different compounds. PPARa is well known as a regulator of nutrient metabolism and energy homoeostasis. Moreover, it is involved in the regulation of inflammation and immune response as well as xenobiotic metabolism [1]. After ligand binding, PPARs bind to the peroxisome proliferator response element in the promoter region of target genes as a heterodimer with retinoid X receptor (RXR). Beside ligands, the receptors interact with a huge number of co-activators and co-repressors. Furthermore, their transcriptional activity can also be modulated by cross-talk between phosphorylation and dephosporylation. The effect of these modifications depends on cellular context, receptor type and residue metabolized [2].PPARa is activated by a wide range of both endogenous and exogenous ligands, such as dietary fatty acids, eicosanoids, hypolipidaemic drugs, phthalates, pesticides, etc. The receptor is highly expressed in tissues with active fatty acid metabolism, such as the liver, heart muscle, intestine and kidney. Inappropriate activation of the receptor during prenatal development by xenobiotics can alter gene expression. ...

show abstract

Time-dependent expression of cytochrome p450 epoxygenases during human prenatal development

Cited by 16 publications

References 25 publications

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

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

Spatio‐Temporal Expression of Peroxisome Proliferator‐Activated Receptor α During Human Prenatal Development

Contact Info

Product

Resources

About