Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells

Autores
Wenker, Shirley Denise; Chamorro, María Eugenia; Vota, Daiana Marina; Callero, Mariana Alejandra; Vittori, Daniela Cecilia; Nesse, Alcira Beatriz
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Erythropoietin (Epo) is known to have a significant role in tissues outside the hematopoietic system. In this work, we investigated the function of Epo in cells of neuronal origin subjected to differentiation. Treatment of SH-SY5Y cells with all-trans-retinoic acid (atRA) generated differentiated neuron-like cells, observed by increased expression of neuronal markers and morphological changes. Exposure of undifferentiated cells to proapoptotic stimuli such as staurosporine, TNF-α, or hypoxia, significantly increased programmed cell death, which was prevented by previous treatment with Epo. In contrast, atRA-differentiated cultures showed cell resistance to apoptosis. No additional effect of Epo was detected in previously differentiated cells. The inhibition of the PI3K/Akt pathway by Ly294002 abrogated the protective effects induced by either Epo or atRA. The effect of atRA was mediated by an increased expression of Bcl-2 whereas the Epo treatment upregulated not only Bcl-2 but also Bcl-xL. This upregulation by Epo was not detected in atRA-differentiated cells, thus confirming the lack of the protective effect of Epo. As expected, assays with AG490, an inhibitor of Jak2, blocked the Epo action only in undifferentiated cells. This reduced neuroprotective function of Epo on SH-SY5Y-differentiated cells could be explained at least in part by downregulation of the Epo receptor expression, which was observed in atRA-differentiated cells. This study shows differential cellular protection induced by Epo at two stages of SH-SY5Y differentiation. The results allow us to suggest that this differential cell behavior can be ascribed to the interaction between atRA and the signaling pathways mediated by Epo.
Fil: Wenker, Shirley Denise. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chamorro, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Vittori, Daniela Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Nesse, Alcira Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
ALL-TRANS-RETINOIC ACID
APOPTOSIS
DIFFERENTIATION
ERYTHROPOIETIN
ERYTHROPOIETIN RECEPTOR
NEUROPROTECTION
SH-SY5Y CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174359
Acceder
id CONICETDig_876ec085deaa36252b42a65b26cbea98
oai_identifier_str oai:ri.conicet.gov.ar:11336/174359
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y CellsWenker, Shirley DeniseChamorro, María EugeniaVota, Daiana MarinaCallero, Mariana AlejandraVittori, Daniela CeciliaNesse, Alcira BeatrizALL-TRANS-RETINOIC ACIDAPOPTOSISDIFFERENTIATIONERYTHROPOIETINERYTHROPOIETIN RECEPTORNEUROPROTECTIONSH-SY5Y CELLShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Erythropoietin (Epo) is known to have a significant role in tissues outside the hematopoietic system. In this work, we investigated the function of Epo in cells of neuronal origin subjected to differentiation. Treatment of SH-SY5Y cells with all-trans-retinoic acid (atRA) generated differentiated neuron-like cells, observed by increased expression of neuronal markers and morphological changes. Exposure of undifferentiated cells to proapoptotic stimuli such as staurosporine, TNF-α, or hypoxia, significantly increased programmed cell death, which was prevented by previous treatment with Epo. In contrast, atRA-differentiated cultures showed cell resistance to apoptosis. No additional effect of Epo was detected in previously differentiated cells. The inhibition of the PI3K/Akt pathway by Ly294002 abrogated the protective effects induced by either Epo or atRA. The effect of atRA was mediated by an increased expression of Bcl-2 whereas the Epo treatment upregulated not only Bcl-2 but also Bcl-xL. This upregulation by Epo was not detected in atRA-differentiated cells, thus confirming the lack of the protective effect of Epo. As expected, assays with AG490, an inhibitor of Jak2, blocked the Epo action only in undifferentiated cells. This reduced neuroprotective function of Epo on SH-SY5Y-differentiated cells could be explained at least in part by downregulation of the Epo receptor expression, which was observed in atRA-differentiated cells. This study shows differential cellular protection induced by Epo at two stages of SH-SY5Y differentiation. The results allow us to suggest that this differential cell behavior can be ascribed to the interaction between atRA and the signaling pathways mediated by Epo.Fil: Wenker, Shirley Denise. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chamorro, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Vittori, Daniela Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Nesse, Alcira Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaWiley-liss, div John Wiley & Sons Inc.2010-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174359Wenker, Shirley Denise; Chamorro, María Eugenia; Vota, Daiana Marina; Callero, Mariana Alejandra; Vittori, Daniela Cecilia; et al.; Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Biochemistry; 110; 1; 5-2010; 151-1610730-2312CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcb.22521/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcb.22521info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:20Zoai:ri.conicet.gov.ar:11336/174359instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:20.949CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
title Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
spellingShingle Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
Wenker, Shirley Denise
ALL-TRANS-RETINOIC ACID
APOPTOSIS
DIFFERENTIATION
ERYTHROPOIETIN
ERYTHROPOIETIN RECEPTOR
NEUROPROTECTION
SH-SY5Y CELLS
title_short Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
title_full Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
title_fullStr Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
title_full_unstemmed Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
title_sort Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells
dc.creator.none.fl_str_mv Wenker, Shirley Denise
Chamorro, María Eugenia
Vota, Daiana Marina
Callero, Mariana Alejandra
Vittori, Daniela Cecilia
Nesse, Alcira Beatriz
author Wenker, Shirley Denise
author_facet Wenker, Shirley Denise
Chamorro, María Eugenia
Vota, Daiana Marina
Callero, Mariana Alejandra
Vittori, Daniela Cecilia
Nesse, Alcira Beatriz
author_role author
author2 Chamorro, María Eugenia
Vota, Daiana Marina
Callero, Mariana Alejandra
Vittori, Daniela Cecilia
Nesse, Alcira Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ALL-TRANS-RETINOIC ACID
APOPTOSIS
DIFFERENTIATION
ERYTHROPOIETIN
ERYTHROPOIETIN RECEPTOR
NEUROPROTECTION
SH-SY5Y CELLS
topic ALL-TRANS-RETINOIC ACID
APOPTOSIS
DIFFERENTIATION
ERYTHROPOIETIN
ERYTHROPOIETIN RECEPTOR
NEUROPROTECTION
SH-SY5Y CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Erythropoietin (Epo) is known to have a significant role in tissues outside the hematopoietic system. In this work, we investigated the function of Epo in cells of neuronal origin subjected to differentiation. Treatment of SH-SY5Y cells with all-trans-retinoic acid (atRA) generated differentiated neuron-like cells, observed by increased expression of neuronal markers and morphological changes. Exposure of undifferentiated cells to proapoptotic stimuli such as staurosporine, TNF-α, or hypoxia, significantly increased programmed cell death, which was prevented by previous treatment with Epo. In contrast, atRA-differentiated cultures showed cell resistance to apoptosis. No additional effect of Epo was detected in previously differentiated cells. The inhibition of the PI3K/Akt pathway by Ly294002 abrogated the protective effects induced by either Epo or atRA. The effect of atRA was mediated by an increased expression of Bcl-2 whereas the Epo treatment upregulated not only Bcl-2 but also Bcl-xL. This upregulation by Epo was not detected in atRA-differentiated cells, thus confirming the lack of the protective effect of Epo. As expected, assays with AG490, an inhibitor of Jak2, blocked the Epo action only in undifferentiated cells. This reduced neuroprotective function of Epo on SH-SY5Y-differentiated cells could be explained at least in part by downregulation of the Epo receptor expression, which was observed in atRA-differentiated cells. This study shows differential cellular protection induced by Epo at two stages of SH-SY5Y differentiation. The results allow us to suggest that this differential cell behavior can be ascribed to the interaction between atRA and the signaling pathways mediated by Epo.
Fil: Wenker, Shirley Denise. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chamorro, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Vittori, Daniela Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Nesse, Alcira Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Erythropoietin (Epo) is known to have a significant role in tissues outside the hematopoietic system. In this work, we investigated the function of Epo in cells of neuronal origin subjected to differentiation. Treatment of SH-SY5Y cells with all-trans-retinoic acid (atRA) generated differentiated neuron-like cells, observed by increased expression of neuronal markers and morphological changes. Exposure of undifferentiated cells to proapoptotic stimuli such as staurosporine, TNF-α, or hypoxia, significantly increased programmed cell death, which was prevented by previous treatment with Epo. In contrast, atRA-differentiated cultures showed cell resistance to apoptosis. No additional effect of Epo was detected in previously differentiated cells. The inhibition of the PI3K/Akt pathway by Ly294002 abrogated the protective effects induced by either Epo or atRA. The effect of atRA was mediated by an increased expression of Bcl-2 whereas the Epo treatment upregulated not only Bcl-2 but also Bcl-xL. This upregulation by Epo was not detected in atRA-differentiated cells, thus confirming the lack of the protective effect of Epo. As expected, assays with AG490, an inhibitor of Jak2, blocked the Epo action only in undifferentiated cells. This reduced neuroprotective function of Epo on SH-SY5Y-differentiated cells could be explained at least in part by downregulation of the Epo receptor expression, which was observed in atRA-differentiated cells. This study shows differential cellular protection induced by Epo at two stages of SH-SY5Y differentiation. The results allow us to suggest that this differential cell behavior can be ascribed to the interaction between atRA and the signaling pathways mediated by Epo.
publishDate 2010
dc.date.none.fl_str_mv 2010-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/174359
Wenker, Shirley Denise; Chamorro, María Eugenia; Vota, Daiana Marina; Callero, Mariana Alejandra; Vittori, Daniela Cecilia; et al.; Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Biochemistry; 110; 1; 5-2010; 151-161
0730-2312
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174359
identifier_str_mv Wenker, Shirley Denise; Chamorro, María Eugenia; Vota, Daiana Marina; Callero, Mariana Alejandra; Vittori, Daniela Cecilia; et al.; Differential Antiapoptotic Effect of Erythropoietin on Undifferentiated and Retinoic Acid-Differentiated SH-SY5Y Cells; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Biochemistry; 110; 1; 5-2010; 151-161
0730-2312
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcb.22521/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/jcb.22521
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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