The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2

This is copy of an article published in the Antioxidants & Redox Signaling © 2013 Mary Ann Liebert, Inc. Antioxidants& Redox Signalingi available online at: http://online.liebertpub.com

Detalles Bibliográficos
Autores: Parada, Esther, Egea, Javier, Buendía, Izaskun, Negredo Madrigal, Pilar, Cunha, Ana C., Cardoso, Silvia, Soares, Miguel P., García López, Manuela
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/662894
Acceso en línea:http://hdl.handle.net/10486/662894
https://dx.doi.org/10.1089/ars.2012.4671
Access Level:acceso abierto
Palabra clave:Receptor nicotinic
Neuroprotection
Factor Erythroid
Medicina
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spelling The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2Parada, EstherEgea, JavierBuendía, IzaskunNegredo Madrigal, PilarCunha, Ana C.Cardoso, SilviaSoares, Miguel P.García López, ManuelaReceptor nicotinicNeuroprotectionFactor ErythroidMedicinaThis is copy of an article published in the Antioxidants & Redox Signaling © 2013 Mary Ann Liebert, Inc. Antioxidants& Redox Signalingi available online at: http://online.liebertpub.comWe asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the pharmacologic alpha-7 nicotinic acetylcholine receptor (a7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in photothrombotic stroke in vivo. Results: OHCs exposed to OGD followed by reoxygenation elicited cell death, measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation of a7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by abungarotoxin and by tin–protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO- 1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo reduced the infarct size and improved motor skills in Hmox1lox/lox mice that express normal levels of HO-1, but not in LysMCreHmox1D/D in which HO-1 expression is inhibited in myeloid cells, including the microglia. Innovation: This study suggests the participation of the microglial a7 nAChR in the brain cholinergic anti-inflammatory pathway. Conclusion: Activation of the a7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and oxidative stress, affording neuroprotection under brain ischemic conditions. Antioxid. Redox Signal. 19, 1135–1148This work was supported in part by grants from Spanish Ministry of Science and Innovation Ref. SAF2009-12150 and SAF2012-32223 and the Spanish Ministry of Health (Instituto de Salud Carlos III) RETICS-RD06/0026 to MGL. E.P. and I.B. have a predoctoral fellowship from the Spanish Ministry of Economy. We would also like to thank the Fundacion Teofilo Hernando for its continued support. Funding: Fundac¸ao para a Ciencia e Tecnologia (Portugal) grants to MPS: PTDC/BIABCM/ 101311/2008, PTDC/SAU-FCF/100762/2008, and PTDC/SAU-TOX/116627/2010) and European Community 6th Framework Grant LSH-2005-1.2.5-1 and 7th Framework Grant ERC-2011-AdG. 294709–DAMAGECONTROL. Ana Cunha was supported by a fellowship within the project PTDC/SAU-FCF/100762/2008 awarded to MPSMary Ann Liebert, Inc.Departamento de FarmacologíaDepartamento de Anatomía, Histología y NeurocienciaFacultad de Medicina20132013-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/662894https://dx.doi.org/10.1089/ars.2012.4671reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 294709open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6628942026-06-23T12:46:27Z
dc.title.none.fl_str_mv The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
title The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
spellingShingle The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
Parada, Esther
Receptor nicotinic
Neuroprotection
Factor Erythroid
Medicina
title_short The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
title_full The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
title_fullStr The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
title_full_unstemmed The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
title_sort The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2
dc.creator.none.fl_str_mv Parada, Esther
Egea, Javier
Buendía, Izaskun
Negredo Madrigal, Pilar
Cunha, Ana C.
Cardoso, Silvia
Soares, Miguel P.
García López, Manuela
author Parada, Esther
author_facet Parada, Esther
Egea, Javier
Buendía, Izaskun
Negredo Madrigal, Pilar
Cunha, Ana C.
Cardoso, Silvia
Soares, Miguel P.
García López, Manuela
author_role author
author2 Egea, Javier
Buendía, Izaskun
Negredo Madrigal, Pilar
Cunha, Ana C.
Cardoso, Silvia
Soares, Miguel P.
García López, Manuela
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Farmacología
Departamento de Anatomía, Histología y Neurociencia
Facultad de Medicina
dc.subject.none.fl_str_mv Receptor nicotinic
Neuroprotection
Factor Erythroid
Medicina
topic Receptor nicotinic
Neuroprotection
Factor Erythroid
Medicina
description This is copy of an article published in the Antioxidants & Redox Signaling © 2013 Mary Ann Liebert, Inc. Antioxidants& Redox Signalingi available online at: http://online.liebertpub.com
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/662894
https://dx.doi.org/10.1089/ars.2012.4671
url http://hdl.handle.net/10486/662894
https://dx.doi.org/10.1089/ars.2012.4671
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 294709
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert, Inc.
publisher.none.fl_str_mv Mary Ann Liebert, Inc.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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