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Abstract:

Inflammation is a physiological defense response, but may also represent a potential pathological process in neurological diseases. In this regard, microglia have a crucial role in either progression or amelioration of degenerative neuronal damage. Because of the role of hypoxia in pro-inflammatory mechanisms in the nervous system, and the potential anti-inflammatory protective effect of erythropoietin (Epo), we focused our investigation on the role of this factor on activation of microglia and neuroprotection. Activation of microglial cells (EOC-2) was achieved by chemical hypoxia induced by cobalt chloride (CoCl2) and characterized by increased levels of nitrite, tumor necrosis factor-α and reactive oxygen species production, as well as up-regulation of inducible nitric oxide synthase expression. Under these conditions, cell proliferation data and proliferating cell nuclear antigen (PCNA) staining demonstrated a mitogenic effect of chemical hypoxia. Even though pre-treatment with Epo did not prevent nitrite production, inducible nitric oxide synthase protein expression or tumor necrosis factor-α secretion, it prevented the oxidative stress induced by CoCl2 as well as cell proliferation. Neuronal cells (SH-SY5Y) cultured in the presence of conditioned medium from activated EOC-2 cells or macrophages (RAW 264.7) developed significant apoptosis, an effect that was abolished by Epo via Epo/Epo receptor activation. The results show that even though Epo did not exert a direct anti-inflammatory effect on microglia activation, it did increase the resistance of neurons to subsequent damage from pro-inflammatory agents. In addition to its anti-apoptotic ability, the Epo antioxidant effect may have an indirect influence on neuronal survival by modulation of the pro-inflammatory environment. Neuronal cells (SH-SY5Y) cultured in the presence of conditioned media from activated microglia (EOC-2) or macrophages (RAW 264.7) developed significant apoptosis, induced by high levels of NO, TNF-α, and ROS. This effect was prevented by erythropoietin (Epo) via Epo receptor activation. In addition to its antiapoptotic ability, the Epo antioxidant effect might account for an indirect influence on neuronal survival. © 2013 FEBS.

Registro:

Documento: Artículo
Título:Protective action of erythropoietin on neuronal damage induced by activated microglia
Autor:Wenker, S.D.; Chamorro, M.E.; Vittori, D.C.; Nesse, A.B.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires IQUIBICEN-CONICET (Instituto de Química Biológica, Buenos Aires, C1428EHA, Argentina
Palabras clave:erythropoietin; hypoxia; inflammation; microglia; neuroprotection; cobalt chloride; cycline; erythropoietin; inducible nitric oxide synthase; nitrite; reactive oxygen metabolite; tumor necrosis factor alpha; animal cell; animal experiment; animal model; antiinflammatory activity; antioxidant activity; apoptosis; article; cell activation; cell proliferation; cell survival; controlled study; cytokine release; human; human cell; hypoxia; macrophage; microglia; mouse; nerve cell; nerve cell lesion; neuroprotection; nonhuman; oxidative stress; priority journal; protein expression; upregulation; Animals; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Cobalt; Culture Media, Conditioned; Erythropoietin; Humans; Inflammation; Mice; Microglia; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; Nitric Oxide Synthase Type II; Nitrites; Proliferating Cell Nuclear Antigen; Reactive Oxygen Species; Receptors, Erythropoietin; Tumor Necrosis Factor-alpha
Año:2013
Volumen:280
Número:7
Página de inicio:1630
Página de fin:1642
DOI: http://dx.doi.org/10.1111/febs.12172
Título revista:FEBS Journal
Título revista abreviado:FEBS J.
ISSN:1742464X
CODEN:FJEOA
CAS:cobalt chloride, 1332-82-7, 7646-79-9; erythropoietin, 11096-26-7; inducible nitric oxide synthase, 501433-35-8; nitrite, 14797-65-0; Cobalt, 7440-48-4; Culture Media, Conditioned; Erythropoietin, 11096-26-7; Neuroprotective Agents; Nitric Oxide Synthase Type II, 1.14.13.39; Nitrites; Nos2 protein, mouse, 1.14.13.39; Proliferating Cell Nuclear Antigen; Reactive Oxygen Species; Receptors, Erythropoietin; Tumor Necrosis Factor-alpha; cobaltous chloride, 7646-79-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1742464X_v280_n7_p1630_Wenker

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Citas:

---------- APA ----------
Wenker, S.D., Chamorro, M.E., Vittori, D.C. & Nesse, A.B. (2013) . Protective action of erythropoietin on neuronal damage induced by activated microglia. FEBS Journal, 280(7), 1630-1642.
http://dx.doi.org/10.1111/febs.12172
---------- CHICAGO ----------
Wenker, S.D., Chamorro, M.E., Vittori, D.C., Nesse, A.B. "Protective action of erythropoietin on neuronal damage induced by activated microglia" . FEBS Journal 280, no. 7 (2013) : 1630-1642.
http://dx.doi.org/10.1111/febs.12172
---------- MLA ----------
Wenker, S.D., Chamorro, M.E., Vittori, D.C., Nesse, A.B. "Protective action of erythropoietin on neuronal damage induced by activated microglia" . FEBS Journal, vol. 280, no. 7, 2013, pp. 1630-1642.
http://dx.doi.org/10.1111/febs.12172
---------- VANCOUVER ----------
Wenker, S.D., Chamorro, M.E., Vittori, D.C., Nesse, A.B. Protective action of erythropoietin on neuronal damage induced by activated microglia. FEBS J. 2013;280(7):1630-1642.
http://dx.doi.org/10.1111/febs.12172