Involvement of Bax Protein in the Prevention of Glucocorticoid-Induced Thymocytes Apoptosis by Melatonin

• Autores: Hoijman, E.; Rocha Viegas, L.; Keller Sarmiento, M.I.; Rosenstein, R.E.; Pecci, A.
• Año de publicación: 2004
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Endocrinology 2004;145(1):418-425
• Materia: 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
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

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.
Fil:Hoijman, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Rocha Viegas, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Rosenstein, R.E. 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.