Abstract
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix (bHLH) transcription factor that is activated by environmental contaminants including polychlorinated biphenyls (PCBs). The AHR affects a variety of processes that are involved in cell growth and differentiation. In this study, we constructed a P19 embryonic carcinoma cell line with AHR gene silencing using the vector-based approach of short hairpin (sh)RNA interference that allows cells to differentiate into cardiac myocytes when treated with dimethyl sulfoxide (DMSO). The expression levels of the cardiac development-specific GATA4 and Nkx2.5 genes were measured using real-time quantitative polymerase chain reaction (qPCR). Our data showed that the expression levels of the GATA4 and Nkx2.5 genes were increased in the AHR-silenced P19 cells compared with the control groups. Four critical genes (ARNT, CYP1A1, GSK3β and β-catenin) expressed in the AHR and in the Wnt signaling pathway were also measured by qPCR. We found that the expression levels of ARNT, CYP1A1 and β-catenin were suppressed, whereas GSK3β expression was elevated in the AHR-silenced P19 cells. Therefore, it is possible that the silencing of AHR promotes the differentiation of P19 cells through the AHR and Wnt signal transduction pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aryl Hydrocarbon Receptor Nuclear Translocator / genetics
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Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
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Cell Differentiation / drug effects
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Cells, Cultured
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Cytochrome P-450 CYP1A1 / genetics
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Cytochrome P-450 CYP1A1 / metabolism
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Dimethyl Sulfoxide / pharmacology
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Embryonal Carcinoma Stem Cells / cytology*
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Embryonal Carcinoma Stem Cells / metabolism
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GATA4 Transcription Factor / genetics
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GATA4 Transcription Factor / metabolism
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Homeobox Protein Nkx-2.5
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Myocytes, Cardiac / cytology*
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RNA Interference*
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RNA, Small Interfering / metabolism*
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Receptors, Aryl Hydrocarbon / antagonists & inhibitors
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Wnt Signaling Pathway / drug effects
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Arnt protein, mouse
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GATA4 Transcription Factor
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Gata4 protein, mouse
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Homeobox Protein Nkx-2.5
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Homeodomain Proteins
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Nkx2-5 protein, mouse
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RNA, Small Interfering
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Receptors, Aryl Hydrocarbon
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Transcription Factors
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beta Catenin
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Cytochrome P-450 CYP1A1
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Glycogen Synthase Kinase 3
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Dimethyl Sulfoxide