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The antiapoptotic effect of melatonin (MEL) has been described in several systems. In particular, MEL inhibits glucocorticoid-mediated apoptosis. Our group previously demonstrated that in the thymus, MEL inhibits the release of Cytochrome C from mitochondria and the dexamethasone-dependent increase of bax mRNA levels. In this study we analyzed the ability of MEL to regulate the activation of the glucocorticoid receptor (GR) in mouse thymocytes. We found that even though the methoxyindole does not affect the ligand binding capacity of the receptor, it impairs the steroid-dependent nuclear translocation of the GR and also prevents transformation by blocking the dissociation of the 90-kDa heat shock protein. Coincubation of the methoxyindole with dexamethasone did not affect the expression of a reporter gene in GR-transfected Cos-7 cells or HC11 and L929 mouse cell lines that express Mel-1a and retinoid-related orphan receptor-α (RORα) receptors. Therefore, the antagonistic effect of MEL seems to be specific for thymocytes, in a Mel 1a- and RORα-independent manner. In summary, the present results suggest a novel mechanism for the antagonistic action of MEL on GR-mediated effects, which involves the inhibition of 90-kDa heat shock protein dissociation and the cytoplasmic retention of the GR. Copyright © 2006 by The Endocrine Society.


Documento: Artículo
Título:Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
Autor:Presman, D.M.; Hoijman, E.; Ceballos, N.R.; Galigniana, M.D.; Pecci, A.
Filiación:Inst. de Fisiol., Biologia Molec. Y Neurociencias-Consejo Nac. de Invest. Cientificas Y Tecnicas, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina
Departamento de Fisiologia, Biologia Molecular Y Celular and Biodivesidad Y Biologia Experimental, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina
Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina
IFIBYNE (Inst. de Fisiol., Biologia Molec. Y Neurociencias)-Consejo Nac. de Invest Cientificas/Tec, Departamentos de Quimica Biologica, Fisiologia, Biologia Molecular Y Celular, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Palabras clave:cell nucleus receptor; cytochrome c; dexamethasone; glucocorticoid receptor; heat shock protein 90; indole derivative; melatonin; messenger RNA; methoxyindole; orphan nuclear receptor ROR alpha; protein Bax; retinoid; unclassified drug; animal cell; animal experiment; article; breast epithelium; controlled study; drug inhibition; drug mechanism; gene expression; gene translocation; immunoprecipitation; ligand binding; male; mouse; nonhuman; priority journal; thymocyte; transcription initiation; Active Transport, Cell Nucleus; Animals; Apoptosis; Cell Nucleus; Dexamethasone; Male; Melatonin; Mice; Protein Transport; Receptors, Glucocorticoid; T-Lymphocytes; Thymus Gland
Página de inicio:5452
Página de fin:5459
Título revista:Endocrinology
Título revista abreviado:Endocrinology
CAS:cytochrome c, 9007-43-6, 9064-84-0; dexamethasone, 50-02-2; melatonin, 73-31-4; Dexamethasone, 50-02-2; Melatonin, 73-31-4; Receptors, Glucocorticoid


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---------- APA ----------
Presman, D.M., Hoijman, E., Ceballos, N.R., Galigniana, M.D. & Pecci, A. (2006) . Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes. Endocrinology, 147(11), 5452-5459.
---------- CHICAGO ----------
Presman, D.M., Hoijman, E., Ceballos, N.R., Galigniana, M.D., Pecci, A. "Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes" . Endocrinology 147, no. 11 (2006) : 5452-5459.
---------- MLA ----------
Presman, D.M., Hoijman, E., Ceballos, N.R., Galigniana, M.D., Pecci, A. "Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes" . Endocrinology, vol. 147, no. 11, 2006, pp. 5452-5459.
---------- VANCOUVER ----------
Presman, D.M., Hoijman, E., Ceballos, N.R., Galigniana, M.D., Pecci, A. Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes. Endocrinology. 2006;147(11):5452-5459.