INVESTIGADORES
PREGI Nicolas
congresos y reuniones científicas
Título:
Erythropoietin neuroprotective effect on SHSY-5Y cellsninduced to apoptosis by TNF-alpha.
Autor/es:
PREGI N; WENKER S; CHAMORRO ME; PÉREZ LEIRÓS C; NESE A
Lugar:
Pinamar, Argentina
Reunión:
Congreso; X Panamerican Association for Biochemistry and Molecular Biology Congress and XX Annual Meeting of Sociedad Argentina de Neuroquímica; 2005
Resumen:
The human
neuroblastoma SH-SY5Y cells are an excellent model for the study of
neuroprotection induced by treatment with human recombinant erythropoietin
(Epo). We investigated signaling pathways involved in this Epo effect in a
model of apoptosis induced by tumor necrosis factor-alpha (TNF). Apoptosis of SH-SY5Y
cells was developed by addition of 25 ng/ml TNF for 24 h and detected by
typical morphological changes (Hoechst staining) and DNA laddering. Under this
condition, a decrease in Epo receptor (EpoR) expression was observed at mRNA
and protein levels, assayed by RT-PCR and Western blot, respectively. The
pre-treatment for 12 h with 25 U/ml Epo attenuated the signs of apoptosis observed
under the effect of TNF while the levels of
EpoR expression was recovered. An
increased expression of bcl-2 at mRNA and protein levels, but no changes in
bcl-x, bax and c-Flip mRNA levels were also detected. An assay in the presence of
the inhibitor wortmannin showed that the antiapoptotic effect of Epo was, at
least in part, mediated by PI3K.
In
conclusion, the results show an Epo neuroprotective capacity to antagonize
TNF-induced apoptosis in SHSY5Y cells, action that is partially dependent on
the modulation of EpoR and also associated with the increased expression of the
antiapoptotic protein Bcl-2.