Melatonin inhibits the nuclear translocation of the glucocorticoid receptor (GR): an answer to its anti-apoptotic effect on mouse thymocytes

PRESMAN DM, CEBALLOS NR, GALIGNIANA MD, PECCI A.

Buenos Aires

Congreso; X Congress of the Panamerican Association for Biochemistry & Molecular Biology/SAIB; 2006

In previous works, our group have demonstrated that the antagonistic effect of melatonin on the glucocorticoid-mediated apoptosis on mouse thymocytes involves the prevention of cytochrome C release and a decrease in bax expression. Despite that several reports have shown the antagonism melatonin/ glucocorticoid, little is known about the molecular mechanisms involved on this process. In the present work we analysed the ability of melatonin to modulate GR activation. We found, by performing competence assays that melatonin does not affect the binding of dexamethasone to GR. However, according to immunofluorescence confocal microscopy and subcellular fractionation followed by western-blot assays, melatonin prevents the dexamethasone-mediated GR nuclear translocation. Moreover, we also observed, by co-immunoprecipitation experiments, that the methoxyindole completely blocks the GR/Hsp90 disssociation. Theses effects seem to be tissue-specific as it does not occur on another cell types like HC11 and Cos-7 cell lines. Taken together the results suggest that melatonin is working as a modifier that influences the transformation of GR upon hormone induction, in a tissue specific manner.