Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes

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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...

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Autores principales:	Presman, D.M., Hoijman, E., Ceballos, N.R., Galigniana, M.D., Pecci, A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2006
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v147_n11_p5452_Presman
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_00137227_v147_n11_p5452_Presman2023-06-12T16:41:38Z Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes Endocrinology 2006;147(11):5452-5459 Presman, D.M. Hoijman, E. Ceballos, N.R. Galigniana, M.D. Pecci, A. 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 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. Fil:Presman, D.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Hoijman, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ceballos, N.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pecci, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v147_n11_p5452_Presman
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	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
spellingShingle	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 Presman, D.M. Hoijman, E. Ceballos, N.R. Galigniana, M.D. Pecci, A. Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
topic_facet	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
description	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.
format	Artículo Artículo publishedVersion
author	Presman, D.M. Hoijman, E. Ceballos, N.R. Galigniana, M.D. Pecci, A.
author_facet	Presman, D.M. Hoijman, E. Ceballos, N.R. Galigniana, M.D. Pecci, A.
author_sort	Presman, D.M.
title	Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
title_short	Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
title_full	Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
title_fullStr	Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
title_full_unstemmed	Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
title_sort	melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes
publishDate	2006
url	http://hdl.handle.net/20.500.12110/paper_00137227_v147_n11_p5452_Presman
work_keys_str_mv	AT presmandm melatonininhibitsglucocorticoidreceptornucleartranslocationinmousethymocytes AT hoijmane melatonininhibitsglucocorticoidreceptornucleartranslocationinmousethymocytes AT ceballosnr melatonininhibitsglucocorticoidreceptornucleartranslocationinmousethymocytes AT galignianamd melatonininhibitsglucocorticoidreceptornucleartranslocationinmousethymocytes AT peccia melatonininhibitsglucocorticoidreceptornucleartranslocationinmousethymocytes
_version_	1769810071940759552

Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes

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