CONICET | Buscador de Institutos y Recursos Humanos

Erythropoietin (Epo) has emerged as a multifunctional factor that could play an important role in tissues outside the hematopoietic system. In previous works, we found an Epo antiapoptotic action on undifferentiated neuronal SH-SY5Y cells against cytotoxicity induced by stauroporine (STP) or TNF-alpha. Then, we investigated whether the protective effect of Epo could be detected in neuronal cells differentiated by retinoic acid (RA). Immature and mature stages of SH-SY5Y cells were exposed to proapoptotic agents. Morphological changes were observed by scanning electron microscopy. STP, TNF-alpha and hypoxia significantly reduced cell viability (MTT assay) and increased apoptosis (Hoechst staining) in immature cell cultures (STP 49±3%, TNF 49±3%, H 28±2%, P<0.05 vs. Control). However, resistance was observed in RA-differentiated cells (RA-STP 28±3%, RA-TNF 15±3%, RA-H 7±2%, P<0.05 vs. Control). Pretreatment of undifferentiated cells with Epo significantly prevented cell death against STP (23±3%), TNF (20±6%), or hypoxia (7±2%). These effects can be partially explained by Bcl-xL upregulation while Bcl-2 and Bax seem not to be modulated (RT-PCR). After short periods of hypoxia Epo was able to revert cell damages. Instead, no additional effect of Epo was observed upon differentiated cells, which might be associated to downregulation of the erythropoietin receptor expression. In conclusion, Epo is able to protect immature SH-SY5Y cells from cell death induced by STP, TNF-alpha or hypoxia and to overcome deleterious effects of acute hypoxia. The results also suggest that the neuroprotective action of Epo depends on the degree of cell differentiation. This differential behavior of immature and mature neuronal cells could be important in the pharmacological effect of Epo.

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