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Autor(en) / Beteiligte
Titel
Melatonin inhibits glucocorticoid-dependent GR–TIF2 interaction in newborn hamster kidney (BHK) cells
Ist Teil von
  • Molecular and cellular endocrinology, 2012-02, Vol.349 (2), p.214-221
Ort / Verlag
Ireland: Elsevier Ireland Ltd
Erscheinungsjahr
2012
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • ► Mechanisms involved on the glucocorticoid–melatonin antagonism in BHK cells. ► Melatonin impairs GR interaction with TIF2 coactivator in BHK cells. ► Antiglucocorticoid effects of the methoxyindol luzindole. The antagonism exerted by melatonin on the glucocorticoid response has been well established, being strongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoid receptor (GR) dissociation from the chaperone hetero-complex and nuclear translocation on mouse thymocytes. Here, by performing confocal fluorescence microscopy and the Number and Brightness assay we show that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocation nor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrations of melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). This melatonin effect was not blocked by the MT1/MT2 receptor antagonist luzindole. Curiously, luzindole behaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven gene expression affecting neither GR translocation nor GR–TIF2 interaction.

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