The aryl hydrocarbon receptor and retinoid receptors cross-talk at the CYP1A1 promoter in vitro

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dc.contributor.authorHessel-Pras, Stefanie
dc.contributor.authorEhlers, Anke
dc.contributor.authorBraeuning, Albert
dc.contributor.authorLampen, Alfonso
dc.date.accessioned2018-06-15T12:14:49Z
dc.date.available2018-06-15T12:14:49Z
dc.date.issued2018-03-15
dc.description.abstractThe epithelium of the small intestine plays an important role in detoxification processes due to the presence of various xenobiotic-metabolizing enzymes from phase I and II, as well as transport proteins of the ATP-binding cassette superfamily. Exposure to xenobiotics induces the expression of these proteins in the small intestine, with multiple signaling pathways stimulated by exogenous compounds converging at individual gene promoters by mechanisms which have not been fully understood yet. In this context the promoter region of the CYP1A1 gene, encoding the phase I monooxygenase cytochrome P450 1A1, was analyzed by chromatin immunoprecipitation with regard to binding of xeno-sensing receptors following stimulation of Caco-2 cells with agonists of the aryl hydrocarbon receptor (AHR) and retinoid receptors. Histone acetylation in the regulatory region of CYP1A1 was enhanced by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or all-trans retinoic acid (at-RA). Binding of retinoid-X-receptor (RXR) α to the promoter region was detected in response to at-RA, while AHR bound to the gene promoter following its activation by TCDD. Of note, enhanced RXRα binding was also detected after AHR stimulation, and increased AHR binding was observed after retinoid receptor activation by at-RA. Exposure of Caco-2 cells to mixtures of AHR and retinoid receptor agonists yielded synergistic induction of CYP1A1 mRNA. In conclusion, the present data improve our knowledge on retinoic acid-dependent effects on CYP1A1 expression and demonstrate unexpected mixture effects by cross-talk of the different receptors.en
dc.identifier.citationEXCLI Journal 2018;17:246-256de
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/36921
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-18920
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 17 2018
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCytochrome P450en
dc.subjectDioxinen
dc.subjectDrug metabolismen
dc.subjectEnzyme inductionen
dc.subjectRXRen
dc.subject.ddc610
dc.titleThe aryl hydrocarbon receptor and retinoid receptors cross-talk at the CYP1A1 promoter in vitroen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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