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Abstract:

It is now recognized that in addition to its activity upon erythroid progenitor cells, erythropoietin (Epo) is capable of stimulating survival of different non-erythroid cells. Since stimulation of erythropoiesis is unwanted for neuroprotection, Epo-like compounds with a more selective action are under investigation. Although the carbamylated derivative of erythropoietin (cEpo) has demonstrated non-hematopoietic tissue protection without erythropoietic effect, little is known about differential mechanisms between Epo and cEpo. Therefore, we investigated signaling pathways which play a key role in Epo-induced proliferation. Here we show that cEpo blocked FOXO3a phosphorylation, allowing expression of downstream target p27kip1 in UT-7 and TF-1 cells capable of erythroid differentiation. This is consistent with the involvement of cEpo in slowing down G1-to-S-phase progression compared with the effect of Epo upon cell cycle. In contrast, similar antiapoptotic actions of cEpo and Epo were observed in neuronal SH-SY5Y cells. Inhibition and competition assays suggest that Epo may act through both, the homodimeric (EpoR/EpoR) and the heterodimeric (EpoR/βcR) receptors in neuronal SH-SY5Y cells and probably in the TF-1 cell type as well. Results also indicate that cEpo needs both the EpoR and βcR subunits to prevent apoptosis of neuronal cells. Based on evidence suggesting that cell proliferation pathways were involved in the differential effect of Epo and cEpo, we went forward to studying downstream signals. Here we provide the first evidence that unlike Epo, cEpo failed to induce FOXO3a inactivation and subsequent p27kip1 downregulation, which is clearly shown in the incapacity of cEpo to induce erythroid cell growth. © 2013 Elsevier B.V.

Registro:

Documento: Artículo
Título:Signaling pathways of cell proliferation are involved in the differential effect of erythropoietin and its carbamylated derivative
Autor:Chamorro, M.E.; Wenker, S.D.; Vota, D.M.; Vittori, D.C.; Nesse, A.B.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina
Pabellón II, Ciudad Universitariam Piso 4, Ciudad Autónoma de Buenos Aires C1428EHA, Argentina
Palabras clave:Carbamylated erythropoietin; Cell cycle; Cell proliferation; Erythropoietin; FOXO3a; P27kip1; carbamylated derivative of erythropoietin; cyclin dependent kinase inhibitor 1B; erythropoietin; transcription factor FKHRL1; unclassified drug; apoptosis; article; cell cycle G1 phase; cell cycle progression; cell cycle S phase; cell differentiation; cell proliferation; controlled study; human; human cell; neuroblastoma cell; priority journal; protein expression; protein phosphorylation; signal transduction; Apoptosis; Cell Differentiation; Cell Growth Processes; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p27; Erythroid Cells; Erythropoiesis; Erythropoietin; Forkhead Transcription Factors; G1 Phase; Humans; Neurons; Phosphorylation; Receptors, Erythropoietin; S Phase; Signal Transduction
Año:2013
Volumen:1833
Número:8
Página de inicio:1960
Página de fin:1968
DOI: http://dx.doi.org/10.1016/j.bbamcr.2013.04.006
Título revista:Biochimica et Biophysica Acta - Molecular Cell Research
Título revista abreviado:Biochim. Biophys. Acta Mol. Cell Res.
ISSN:01674889
CODEN:BAMRD
CAS:erythropoietin, 11096-26-7; CDKN1B protein, human; Cyclin-Dependent Kinase Inhibitor p27, 147604-94-2; Erythropoietin, 11096-26-7; FOXO3 protein, human; Forkhead Transcription Factors; Receptors, Erythropoietin; carbamylated erythropoietin
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_01674889_v1833_n8_p1960_Chamorro.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01674889_v1833_n8_p1960_Chamorro

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Citas:

---------- APA ----------
Chamorro, M.E., Wenker, S.D., Vota, D.M., Vittori, D.C. & Nesse, A.B. (2013) . Signaling pathways of cell proliferation are involved in the differential effect of erythropoietin and its carbamylated derivative. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(8), 1960-1968.
http://dx.doi.org/10.1016/j.bbamcr.2013.04.006
---------- CHICAGO ----------
Chamorro, M.E., Wenker, S.D., Vota, D.M., Vittori, D.C., Nesse, A.B. "Signaling pathways of cell proliferation are involved in the differential effect of erythropoietin and its carbamylated derivative" . Biochimica et Biophysica Acta - Molecular Cell Research 1833, no. 8 (2013) : 1960-1968.
http://dx.doi.org/10.1016/j.bbamcr.2013.04.006
---------- MLA ----------
Chamorro, M.E., Wenker, S.D., Vota, D.M., Vittori, D.C., Nesse, A.B. "Signaling pathways of cell proliferation are involved in the differential effect of erythropoietin and its carbamylated derivative" . Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1833, no. 8, 2013, pp. 1960-1968.
http://dx.doi.org/10.1016/j.bbamcr.2013.04.006
---------- VANCOUVER ----------
Chamorro, M.E., Wenker, S.D., Vota, D.M., Vittori, D.C., Nesse, A.B. Signaling pathways of cell proliferation are involved in the differential effect of erythropoietin and its carbamylated derivative. Biochim. Biophys. Acta Mol. Cell Res. 2013;1833(8):1960-1968.
http://dx.doi.org/10.1016/j.bbamcr.2013.04.006