Open AccessAn evidence for regulatory cross-talk between aryl hydrocarbon receptor and glucocorticoid receptor in HepG2 cells
Author(s) -
Zdeněk Dvořák,
R Vrzal,
Petr Pávek,
J Ulrichová
Publication year - 2008
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/a10.33549/physiolres.931090
Subject(s) - aryl hydrocarbon receptor , glucocorticoid receptor , receptor , microbiology and biotechnology , downregulation and upregulation , signal transduction , nuclear receptor , glucocorticoid , regulation of gene expression , transcriptional regulation , gene expression , biology , chemistry , transcription factor , gene , biochemistry , endocrinology
Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)play crucial role in the regulation of drug metabolizing enzymesand in many essential physiological processes. Cellular signalingby these receptors shares several functional and regulatoryfeatures. Here we investigated regulatory cross-talk betweenthese two receptors. Human hepatoma cells (HepG2) were themodel of choice. We analyzed the effects of dexamethasone(DEX) and dioxin (TCDD) on i) expression of AhR and GRαmRNAs; ii) levels of AhR and GR proteins; iii) transcriptionalactivities of AhR and GR in reporter assays; iv) 7-ethoxyresorufinO-deethylase activity (EROD). We found that both DEX and TCDDaffected AhR and GR mRNAs expression, proteins levels andtranscriptional activities in HepG2 cells. These effects on cellularsignaling by AhR and GR comprised up-/down-regulation of geneexpression and ligand-dependent protein degradation. Weconclude that interactive regulatory cross-talk between GR andAhR receptors in HepG2 cells defines possible implications inphysiology and drug metabolism. Future research should befocused on the investigation of AhR-GR cross-talk in variousnormal human cells and tissues both in vitro and in vivo.