Crosstalk between activated forms of the aryl hydrocarbon receptor and glucocorticoid receptor |
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Authors: | Shao-Hung Wang Chu-Ting Liang Yi-Wen Liu Min-Cong Huang See-Chang Huang Wei-Fu Hong Jyan-Gwo J. Su |
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Affiliation: | 1. Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, ROC;2. Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan, ROC;3. Graduate Institute of Biomedical and Biopharmaceutical Sciences, National Chiayi University, Chiayi 600, Taiwan, ROC;4. Cell Engineering Lab, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu 310, Taiwan, ROC;5. Department of Biological Resources, National Chiayi University, Chiayi 600, Taiwan, ROC |
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Abstract: | Pyrene, benzo[a]pyrene (BaP), and indeno[1,2,3-cd]pyrene (IND) are poly cyclic aromatic hydrocarbons (PAHs) with four to six annealed phenyl rings. Dexamethasone (Dex) is a synthetic agonist of glucocorticoids. The aryl hydrocarbon receptor (AhR) ligands, BaP and IND, did not directly activate the glucocorticoid receptor (GR), and Dex did not activate the AhR either. Whenever BaP and IND were added to Dex-treated cultures, they were present with Dex for longer periods, and higher enhancement of Dex-induced transactivation of the GR was found, which indicates that the freshly activated AhR is essential for synergistic interactions with the activated GR. The degree of enhancement of Dex-induced transactivation of the GR by PAHs, BaP ≈ IND > pyrene, paralleled the potency of PAHs in activating the AhR. This synergistic interaction was more distinct in ovarian granulosa cells (HO23) than in HepG2, 293T, or HeLa cells. In contrast, Dex suppressed AhR-mediated expressions, including AhR and cytochrome P450 (CYP) 1 A1 expressions. Dex also counteracted the BaP-induced decrease in cell viability. Crosstalk between the AhR and GR was independent of their expression levels. We concluded that the AhR functionally cross-reacts with the GR, through which transactivation activity of the GR is further enhanced, and in contrast, transactivation activity of the AhR is inhibited. This report shows the significance of in vitro endocrine-related results, which provide a clue for molecular studies of an interactive mechanism between the AhR and GR, and should be confirmed by future in vivo studies. |
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Keywords: | AhR, aryl hydrocarbon receptor AHRE, aryl hydrocarbon response element Ant, anthracene BaP, benzo[a]pyrene Ben, benzene CYP, cytochrome P450 Dex, dexamethasone DMSO, dimethyl sulfoxide EtOH, ethanol GR, glucocorticoid receptor GRE, glucocorticoid receptor response element IND, indeno[1,2,3-cd]pyrene MMTV-LTR, mouse mammary tumor virus long-terminal repeat NP, naphthalene PAHs, polycyclic aromatic hydrocarbons Py, pyrene |
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