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Abstract:

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.

Registro:

Documento: Artículo
Título:c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis
Autor:Vittori, D.; Vota, D.; Callero, M.; Chamorro, M.E.; Nesse, A.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabelló n II, Piso 4, Ciudad de Buenos Aires (C1428EHA), Argentina
Palabras clave: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
Año:2010
Volumen:34
Número:6
Página de inicio:621
Página de fin:630
DOI: http://dx.doi.org/10.1042/CBI20090085
Título revista:Cell Biology International
Título revista abreviado:Cell Biol. Int.
ISSN:10656995
CODEN:CBIIE
CAS:erythropoietin, 11096-26-7; hemin, 16009-13-5; phosphatidylinositol 3 kinase, 115926-52-8; 1-Phosphatidylinositol 3-Kinase, 2.7.1.137; CASP8 and FADD-Like Apoptosis Regulating Protein; CFLAR protein, human; Erythropoietin, 11096-26-7; Hemin, 16009-13-5; Tumor Necrosis Factor-alpha
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10656995_v34_n6_p621_Vittori

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Citas:

---------- APA ----------
Vittori, D., Vota, D., Callero, M., Chamorro, M.E. & Nesse, A. (2010) . c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis. Cell Biology International, 34(6), 621-630.
http://dx.doi.org/10.1042/CBI20090085
---------- CHICAGO ----------
Vittori, D., Vota, D., Callero, M., Chamorro, M.E., Nesse, A. "c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis" . Cell Biology International 34, no. 6 (2010) : 621-630.
http://dx.doi.org/10.1042/CBI20090085
---------- MLA ----------
Vittori, D., Vota, D., Callero, M., Chamorro, M.E., Nesse, A. "c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis" . Cell Biology International, vol. 34, no. 6, 2010, pp. 621-630.
http://dx.doi.org/10.1042/CBI20090085
---------- VANCOUVER ----------
Vittori, D., Vota, D., Callero, M., Chamorro, M.E., Nesse, A. c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-α-induced apoptosis. Cell Biol. Int. 2010;34(6):621-630.
http://dx.doi.org/10.1042/CBI20090085