Effect of erythropoietin on staurosporine-induced apoptosis and differentiation of SH-SY5Y neuroblastoma cells

Since apoptosis appeared to be related to neurodegenerative processes, neuroprotection has been involved in investigation of therapeutic approaches focused upon pharmacological agents to prevent neuronal programmed cell death. In this regard, erythropoietin (Epo) seems to play a critical role. The p...

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Detalles Bibliográficos
Autores: Pregi, N., Vittori, D., Pérez, G., Leirós, C.P., Nesse, A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2006
País:Argentina
Institución:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Repositorio:Biblioteca Digital (UBA-FCEN)
Idioma:inglés
OAI Identifier:paperaa:paper_01674889_v1763_n2_p238_Pregi
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_01674889_v1763_n2_p238_Pregi
Access Level:acceso abierto
Palabra clave:Apoptosis
Bcl-X
Erythropoietin
Neuroprotection
SH-SY5Y cell
Staurosporine
erythropoietin
protein bcl xl
staurosporine
apoptosis
article
cell death
cell differentiation
cell growth
cell structure
controlled study
human
human cell
immunoprecipitation
neurite
neuroblastoma cell
priority journal
reverse transcription polymerase chain reaction
Western blotting
bcl-X Protein
Blotting, Western
Cell Differentiation
Dose-Response Relationship, Drug
Electrophoresis
Enzyme Inhibitors
Erythropoietin, Recombinant
Humans
Kinetics
Microscopy, Fluorescence
Neuroblastoma
Precipitin Tests
Receptors, Erythropoietin
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Descripción
Sumario:Since apoptosis appeared to be related to neurodegenerative processes, neuroprotection has been involved in investigation of therapeutic approaches focused upon pharmacological agents to prevent neuronal programmed cell death. In this regard, erythropoietin (Epo) seems to play a critical role. The present work was focused on the study of the Epo protective effect upon human neuroblastoma SH-SY5Y cells subjected to differentiation by staurosporine. Under this condition, profuse neurite outgrowth was accompanied by programmed cell death (35% of apoptotic cells by Hoechst assay, showing characteristic DNA ladder pattern). A previous treatment with recombinant human Epo (rHuEpo) increased the expression of the specific receptor for Epo while prevented apoptosis. Simultaneously, morphological changes in neurite elongation and interconnection induced by staurosporine were blocked by Epo. These Epo effects proved to be associated to the induction of Bcl-xL at the mRNA and protein levels (RT-PCR and Western blot after immunoprecipitation) and were mediated by activation of pathways inhibited by wortmannin. In conclusion, the fact that both events induced by staurosporine, cell apoptosis and differentiation, were prevented in SH-SY5Y cells previously exposed to rHuEpo suggests interrelated signaling pathways triggered by the Epo/EpoR interaction. © 2005 Elsevier B.V. All rights reserved.