c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis

The TNF-α (tumour necrosis factor) affects a wide range of biological activities, such as cell proliferation and apoptosis. Cell life or death responses to this cytokine might depend on cell conditions. This study focused on the modulation of factors that would affect the sensitivity of erythroid-di...

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Autores principales:	Vittori, Daniela Cecilia, Vota, Daiana Marina, Callero, Mariana A., Chamorro, María Eugenia, Nesse, Alcira Beatriz
Publicado:	2010
Materias:	Cellular FLICE-inhibitory protein (c-FLIP) Erythroid differentiation Erythropoietin K562 cells Tumour necrosis factor-α (TNF-α) UT-7 cell erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha CFLAR protein, human apoptosis article cell differentiation cell growth cell proliferation cell strain K 562 cell survival cell type controlled study down regulation erythroid cell human human cell protein expression protein function signal transduction cytology drug effect genetics metabolism tumor cell line 1-Phosphatidylinositol 3-Kinase Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Cell Differentiation Cell Line, Tumor Down-Regulation Erythroid Cells Hemin Humans K562 Cells Signal Transduction Tumor Necrosis Factor-alpha
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10656995_v34_n6_p621_Vittori http://hdl.handle.net/20.500.12110/paper_10656995_v34_n6_p621_Vittori
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_10656995_v34_n6_p621_Vittori2023-06-08T16:04:15Z c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis Vittori, Daniela Cecilia Vota, Daiana Marina Callero, Mariana A. Chamorro, María Eugenia Nesse, Alcira Beatriz Cellular FLICE-inhibitory protein (c-FLIP) Erythroid differentiation Erythropoietin K562 cells Tumour necrosis factor-α (TNF-α) UT-7 cell erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha CFLAR protein, human erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha apoptosis article cell differentiation cell growth cell proliferation cell strain K 562 cell survival cell type controlled study down regulation erythroid cell human human cell protein expression protein function signal transduction cell differentiation cytology drug effect genetics metabolism tumor cell line 1-Phosphatidylinositol 3-Kinase Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Cell Differentiation Cell Line, Tumor Down-Regulation Erythroid Cells Erythropoietin Hemin Humans K562 Cells Signal Transduction Tumor Necrosis Factor-alpha The TNF-α (tumour necrosis factor) affects a wide range of biological activities, such as cell proliferation and apoptosis. Cell life or death responses to this cytokine might depend on cell conditions. This study focused on the modulation of factors that would affect the sensitivity of erythroid-differentiated cells to TNF-α. Hemin-differentiated K562 cells showed higher sensitivity to TNF-induced apoptosis than undifferentiated cells. At the same time, hemin-induced erythroid differentiation reduced c-FLIP (cellular FLICE-inhibitory protein) expression. However, this negative effect was prevented by prior treatment with Epo (erythropoietin), which allowed the cell line to maintain c-FLIP levels. On the other hand, erythroiddifferentiated UT-7 cells - dependent on Epo for survival - showed resistance to TNF-α pro-apoptotic action. Only after the inhibition of PI3K (phosphatidylinositol-3 kinase)-mediated pathways, which was accompanied by negative c-FLIP modulation and increased erythroid differentiation, were UT-7 cells sensitive to TNF-α-triggered apoptosis. In summary, erythroid differentiation might deregulate the balance between growth promotion and death signals induced by TNF-α, depending on cell type and environmental conditions. The role of c-FLIP seemed to be critical in the protection of erythroiddifferentiated cells from apoptosis or in the determination of their sensitivity to TNF-mediated programmed cell death. Epo, which for the first time was found to be involved in the prevention of c-FLIP down-regulation, proved to have an antiapoptotic effect against the pro-inflammatory factor. The identification of signals related to cell life/death switching would have significant implications in the control of proliferative diseases and would contribute to the understanding of mechanisms underlying the anaemia associated with inflammatory processes. © The Author(s) Journal compilation © 2010 Portland Press Limited. Fil:Vittori, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vota, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Callero, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Chamorro, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Nesse, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10656995_v34_n6_p621_Vittori http://hdl.handle.net/20.500.12110/paper_10656995_v34_n6_p621_Vittori
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Cellular FLICE-inhibitory protein (c-FLIP) Erythroid differentiation Erythropoietin K562 cells Tumour necrosis factor-α (TNF-α) UT-7 cell erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha CFLAR protein, human erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha apoptosis article cell differentiation cell growth cell proliferation cell strain K 562 cell survival cell type controlled study down regulation erythroid cell human human cell protein expression protein function signal transduction cell differentiation cytology drug effect genetics metabolism tumor cell line 1-Phosphatidylinositol 3-Kinase Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Cell Differentiation Cell Line, Tumor Down-Regulation Erythroid Cells Erythropoietin Hemin Humans K562 Cells Signal Transduction Tumor Necrosis Factor-alpha
spellingShingle	Cellular FLICE-inhibitory protein (c-FLIP) Erythroid differentiation Erythropoietin K562 cells Tumour necrosis factor-α (TNF-α) UT-7 cell erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha CFLAR protein, human erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha apoptosis article cell differentiation cell growth cell proliferation cell strain K 562 cell survival cell type controlled study down regulation erythroid cell human human cell protein expression protein function signal transduction cell differentiation cytology drug effect genetics metabolism tumor cell line 1-Phosphatidylinositol 3-Kinase Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Cell Differentiation Cell Line, Tumor Down-Regulation Erythroid Cells Erythropoietin Hemin Humans K562 Cells Signal Transduction Tumor Necrosis Factor-alpha Vittori, Daniela Cecilia Vota, Daiana Marina Callero, Mariana A. Chamorro, María Eugenia Nesse, Alcira Beatriz c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
topic_facet	Cellular FLICE-inhibitory protein (c-FLIP) Erythroid differentiation Erythropoietin K562 cells Tumour necrosis factor-α (TNF-α) UT-7 cell erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha CFLAR protein, human erythropoietin FLICE inhibitory protein hemin phosphatidylinositol 3 kinase tumor necrosis factor alpha apoptosis article cell differentiation cell growth cell proliferation cell strain K 562 cell survival cell type controlled study down regulation erythroid cell human human cell protein expression protein function signal transduction cell differentiation cytology drug effect genetics metabolism tumor cell line 1-Phosphatidylinositol 3-Kinase Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein Cell Differentiation Cell Line, Tumor Down-Regulation Erythroid Cells Erythropoietin Hemin Humans K562 Cells Signal Transduction Tumor Necrosis Factor-alpha
description	The TNF-α (tumour necrosis factor) affects a wide range of biological activities, such as cell proliferation and apoptosis. Cell life or death responses to this cytokine might depend on cell conditions. This study focused on the modulation of factors that would affect the sensitivity of erythroid-differentiated cells to TNF-α. Hemin-differentiated K562 cells showed higher sensitivity to TNF-induced apoptosis than undifferentiated cells. At the same time, hemin-induced erythroid differentiation reduced c-FLIP (cellular FLICE-inhibitory protein) expression. However, this negative effect was prevented by prior treatment with Epo (erythropoietin), which allowed the cell line to maintain c-FLIP levels. On the other hand, erythroiddifferentiated UT-7 cells - dependent on Epo for survival - showed resistance to TNF-α pro-apoptotic action. Only after the inhibition of PI3K (phosphatidylinositol-3 kinase)-mediated pathways, which was accompanied by negative c-FLIP modulation and increased erythroid differentiation, were UT-7 cells sensitive to TNF-α-triggered apoptosis. In summary, erythroid differentiation might deregulate the balance between growth promotion and death signals induced by TNF-α, depending on cell type and environmental conditions. The role of c-FLIP seemed to be critical in the protection of erythroiddifferentiated cells from apoptosis or in the determination of their sensitivity to TNF-mediated programmed cell death. Epo, which for the first time was found to be involved in the prevention of c-FLIP down-regulation, proved to have an antiapoptotic effect against the pro-inflammatory factor. The identification of signals related to cell life/death switching would have significant implications in the control of proliferative diseases and would contribute to the understanding of mechanisms underlying the anaemia associated with inflammatory processes. © The Author(s) Journal compilation © 2010 Portland Press Limited.
author	Vittori, Daniela Cecilia Vota, Daiana Marina Callero, Mariana A. Chamorro, María Eugenia Nesse, Alcira Beatriz
author_facet	Vittori, Daniela Cecilia Vota, Daiana Marina Callero, Mariana A. Chamorro, María Eugenia Nesse, Alcira Beatriz
author_sort	Vittori, Daniela Cecilia
title	c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
title_short	c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
title_full	c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
title_fullStr	c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
title_full_unstemmed	c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
title_sort	c-flip is involved in erythropoietin-mediated protection of erythroid-differentiated cells from tnf-α-induced apoptosis
publishDate	2010
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10656995_v34_n6_p621_Vittori http://hdl.handle.net/20.500.12110/paper_10656995_v34_n6_p621_Vittori
work_keys_str_mv	AT vittoridanielacecilia cflipisinvolvedinerythropoietinmediatedprotectionoferythroiddifferentiatedcellsfromtnfainducedapoptosis AT votadaianamarina cflipisinvolvedinerythropoietinmediatedprotectionoferythroiddifferentiatedcellsfromtnfainducedapoptosis AT calleromarianaa cflipisinvolvedinerythropoietinmediatedprotectionoferythroiddifferentiatedcellsfromtnfainducedapoptosis AT chamorromariaeugenia cflipisinvolvedinerythropoietinmediatedprotectionoferythroiddifferentiatedcellsfromtnfainducedapoptosis AT nessealcirabeatriz cflipisinvolvedinerythropoietinmediatedprotectionoferythroiddifferentiatedcellsfromtnfainducedapoptosis
_version_	1768545154636972032

c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis

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