An evidence for regulatory cross-talk between aryl hydrocarbon receptor and glucocorticoid receptor in HepG2 cells.
Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) play crucial role in the regulation of drug metabolizing enzymes and in many essential physiological processes. Cellular signaling by these receptors shares several functional and regulatory features. Here we investigated regulatory cross-talk between these two receptors. Human hepatoma cells (HepG2) were the model of choice. We analyzed the effects of dexamethasone (DEX) and dioxin (TCDD) on i) expression of AhR and GRalpha mRNAs; ii) levels of AhR and GR proteins; iii) transcriptional activities of AhR and GR in reporter assays; iv) 7-ethoxyresorufin-O-deethylase activity (EROD). We found that both DEX and TCDD affected AhR and GR mRNAs expression, proteins levels and transcriptional activities in HepG2 cells. These effects on cellular signaling by AhR and GR comprised up-/down-regulation of gene expression and ligand-dependent protein degradation. We conclude that interactive regulatory cross-talk between GR and AhR receptors in HepG2 cells defines possible implications in physiology and drug metabolism. Future research should be focused on the investigation of AhR-GR cross-talk in various normal human cells and tissues both in vitro and in vivo.
Dvořák
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Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University Olomouc, Hnevotínská 3, Olomouc, Czech Republic. moulin@email.cz
Vrzal
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R
Pávek
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P
Ulrichová
J
J
D051792:Basic Helix-Loop-Helix Proteins; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D010865:Pilot Projects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020239:Receptor Cross-Talk; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D003907:Dexamethasone; D005938:Glucocorticoids; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid; C111235:AHR protein, human; C497713:NR3C1 protein, human; C411470:glucocorticoid receptor alpha