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

Departamento de Química Biológica (E.H., L.R.V., A.P.), Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria, C1428EGA; and Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental (M.I.K.S., R.E.R.), Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires 1428, Argentina

Address all correspondence and requests for reprints to: Adalí Pecci, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Pab. II, 4° P, Ciudad Universitaria (C1428EGA), Buenos Aires 1428, Argentina. E-mail: apecci{at}qb.fcen.uba.ar.

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.

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