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The antiapoptotic effect of melatonin has been described in several systems. In this study, the antagonistic effect of the methoxyindole on dexamethasone-induced apoptosis in mouse thymocytes was examined. Melatonin decreased both DNA fragmentation, and the number of annexin V-positive cells incubated in the presence of dexamethasone. Analysis of the expression of the members of the Bcl-2 family indicated that the synthetic glucocorticoid increased Bax protein levels without affecting the levels of Bcl-2, Bcl-X L, Bcl-X S, or Bak. This effect correlated with an increase in thymocytes bax mRNA levels. Dexamethasone also increased the release of cytochrome C from mitochondria. All of these effects were reduced in the presence of melatonin, which was ineffective per se on these parameters. In addition, the involvement of cAMP on glucocorticoid/melatonin antagonism was examined. Both melatonin and dexamethasone decreased the levels of this nucleotide in mouse thymocytes, indicating that the antagonistic action between both hormones involves a cAMP-independent pathway. In summary, the present results suggest that the antiapoptotic effect of melatonin on glucocorticoid-treated thymocytes would be a consequence of an inhibition of the mitochondrial pathway, presumably through the regulation of Bax protein levels.


Documento: Artículo
Título:Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin
Autor:Hoijman, E.; Rocha Viegas, L.; Keller Sarmiento, M.I.; Rosenstein, R.E.; Pecci, A.
Filiación:Depto. de Quím. Biol., Fac. de Ciencias Exactas y Naturales, Ciudad Universitaria, Argentina
Lab. Neuroquimica Retiniana O., Depto. de Bioquímica Humana, Consejo Nac. de Invest. Cie. Tec., Buenos Aires 1428, Argentina
Depto. de Quim. Biol., Fac. de Ciencias Exactas y Naturales, Ciudad Universitaria (C1428EGA), Buenos Aires 1428, Argentina
Palabras clave:cytochrome c; dexamethasone; DNA fragment; glucocorticoid; lipocortin 5; melatonin; protein Bak; protein Bax; protein bcl 2; protein bcl xl; animal cell; animal experiment; animal model; apoptosis; article; cell death; cellular distribution; controlled study; drug induced disease; enzyme activation; gene overexpression; male; mitochondrial membrane; mouse; nonhuman; outer membrane; priority journal; protein analysis; protein family; protein synthesis regulation; receptor density; thymocyte; thymus; Adjuvants, Immunologic; Animals; Apoptosis; bcl-2-Associated X Protein; Cytochromes c; Dexamethasone; Glucocorticoids; Male; Melatonin; Mice; Mice, Inbred Strains; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Glucocorticoid; RNA, Messenger; Thymus Gland
Página de inicio:418
Página de fin:425
Título revista:Endocrinology
Título revista abreviado:Endocrinology
CAS:cytochrome c, 9007-43-6, 9064-84-0; dexamethasone, 50-02-2; lipocortin 5, 111237-10-6; melatonin, 73-31-4; protein Bak, 166801-28-1; protein bcl 2, 219306-68-0; protein bcl xl, 151033-38-4; Adjuvants, Immunologic; Bax protein, mouse; Cytochromes c, 9007-43-6; Dexamethasone, 50-02-2; Glucocorticoids; Melatonin, 73-31-4; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Receptors, Glucocorticoid; bcl-2-Associated X Protein


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---------- APA ----------
Hoijman, E., Rocha Viegas, L., Keller Sarmiento, M.I., Rosenstein, R.E. & Pecci, A. (2004) . Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin. Endocrinology, 145(1), 418-425.
---------- CHICAGO ----------
Hoijman, E., Rocha Viegas, L., Keller Sarmiento, M.I., Rosenstein, R.E., Pecci, A. "Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin" . Endocrinology 145, no. 1 (2004) : 418-425.
---------- MLA ----------
Hoijman, E., Rocha Viegas, L., Keller Sarmiento, M.I., Rosenstein, R.E., Pecci, A. "Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin" . Endocrinology, vol. 145, no. 1, 2004, pp. 418-425.
---------- VANCOUVER ----------
Hoijman, E., Rocha Viegas, L., Keller Sarmiento, M.I., Rosenstein, R.E., Pecci, A. Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin. Endocrinology. 2004;145(1):418-425.