Protective action of erythropoietin on neuronal damage induced by activated microglia

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...

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Autores principales:	Wenker, S.D., Chamorro, M.E., Vittori, D.C., Nesse, A.B.
Formato:	JOUR
Materias:	erythropoietin hypoxia inflammation microglia neuroprotection cobalt chloride cycline 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 macrophage mouse nerve cell nerve cell lesion 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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_1742464X_v280_n7_p1630_Wenker
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_1742464X_v280_n7_p1630_Wenker
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spelling	todo:paper_1742464X_v280_n7_p1630_Wenker2023-10-03T16:30:21Z Protective action of erythropoietin on neuronal damage induced by activated microglia Wenker, S.D. Chamorro, M.E. Vittori, D.C. Nesse, A.B. 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 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. Fil:Wenker, S.D. 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:Vittori, D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Nesse, A.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1742464X_v280_n7_p1630_Wenker
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Wenker, S.D. Chamorro, M.E. Vittori, D.C. Nesse, A.B. Protective action of erythropoietin on neuronal damage induced by activated microglia
topic_facet	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
description	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.
format	JOUR
author	Wenker, S.D. Chamorro, M.E. Vittori, D.C. Nesse, A.B.
author_facet	Wenker, S.D. Chamorro, M.E. Vittori, D.C. Nesse, A.B.
author_sort	Wenker, S.D.
title	Protective action of erythropoietin on neuronal damage induced by activated microglia
title_short	Protective action of erythropoietin on neuronal damage induced by activated microglia
title_full	Protective action of erythropoietin on neuronal damage induced by activated microglia
title_fullStr	Protective action of erythropoietin on neuronal damage induced by activated microglia
title_full_unstemmed	Protective action of erythropoietin on neuronal damage induced by activated microglia
title_sort	protective action of erythropoietin on neuronal damage induced by activated microglia
url	http://hdl.handle.net/20.500.12110/paper_1742464X_v280_n7_p1630_Wenker
work_keys_str_mv	AT wenkersd protectiveactionoferythropoietinonneuronaldamageinducedbyactivatedmicroglia AT chamorrome protectiveactionoferythropoietinonneuronaldamageinducedbyactivatedmicroglia AT vittoridc protectiveactionoferythropoietinonneuronaldamageinducedbyactivatedmicroglia AT nesseab protectiveactionoferythropoietinonneuronaldamageinducedbyactivatedmicroglia
_version_	1807317933059211264

Protective action of erythropoietin on neuronal damage induced by activated microglia

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