Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels

Inflammation contributes to neurodegeneration in post-ischemic brain, diabetes, and Alzheimer's disease. Participants in this inflammatory response include activation of microglia and astrocytes. We studied the role of microglia treated with amyloid-beta peptide (A beta) on hemichannel activity...

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Autores: SAEZ-CARREÑO, JUAN, BENNET, MICHAEL, EZAN, PASCAL, GIAUME, CHRISTIAN, JIANG, JEAN, NAUS, CHRISTIAN, ORELLANA, JUAN
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:Chile
Idioma:inglés
OAI Identifier:oai:repositorio.anid.cl:10533/196781
Acceso en línea:https://hdl.handle.net/10533/196781
Access Level:acceso abierto
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dc.title.none.fl_str_mv Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
dc.title.journal.none.fl_str_mv JOURNAL OF NEUROCHEMISTRY
dc.title.journalabbreviation.none.fl_str_mv J. Neurochem.
title Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
spellingShingle Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
SAEZ-CARREÑO, JUAN
title_short Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
title_full Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
title_fullStr Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
title_full_unstemmed Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
title_sort Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels
dc.creator.none.fl_str_mv SAEZ-CARREÑO, JUAN
BENNET, MICHAEL
EZAN, PASCAL
GIAUME, CHRISTIAN
JIANG, JEAN
NAUS, CHRISTIAN
ORELLANA, JUAN
author SAEZ-CARREÑO, JUAN
author_facet SAEZ-CARREÑO, JUAN
BENNET, MICHAEL
EZAN, PASCAL
GIAUME, CHRISTIAN
JIANG, JEAN
NAUS, CHRISTIAN
ORELLANA, JUAN
author_role author
author2 BENNET, MICHAEL
EZAN, PASCAL
GIAUME, CHRISTIAN
JIANG, JEAN
NAUS, CHRISTIAN
ORELLANA, JUAN
author2_role author
author
author
author
author
author
description Inflammation contributes to neurodegeneration in post-ischemic brain, diabetes, and Alzheimer's disease. Participants in this inflammatory response include activation of microglia and astrocytes. We studied the role of microglia treated with amyloid-beta peptide (A beta) on hemichannel activity of astrocytes subjected to hypoxia in high glucose. Reoxygenation after 3 h hypoxia in high glucose induced transient astroglial permeabilization via Cx43 hemichannels and reduction in intercellular communication via Cx43 cell-cell channels. Both responses were greater and longer lasting in astrocytes previously exposed for 24 h to conditioned medium from A beta-treated microglia (CM-A beta). The effects of CM-A beta were mimicked by TNF-alpha and IL-1 beta and were abrogated by neutralizing TNF-alpha with soluble receptor and IL-1 beta with a receptor antagonist. Astrocytes under basal conditions protected neurons against hypoxia, but exposure to CM-A beta made them toxic to neurons subjected to a sub-lethal hypoxia/reoxygenation episode, revealing the additive nature of the insults. Astrocytes exposed to CM-A beta induced permeabilization of cortical neurons through activation of neuronal pannexin 1 (Panx1) hemichannels by ATP and glutamate released through astroglial Cx43 hemichannels. In agreement, inhibition of NMDA or P2X receptors only partially reduced the activation of neuronal Panx1 hemichannels and neuronal mortality, but simultaneous inhibition of both receptors completely prevented the neurotoxic response. Therefore, we suggest that responses to ATP and glutamate converge in activation of neuronal Panx1 hemichannels. Thus, we propose that blocking hemichannels expressed by astrocytes and/or neurons in the inflamed nervous system could represent a novel and alternative strategy to reduce neuronal loss in various pathological states including Alzheimer's disease, diabetes and ischemia.
publishDate 2011
dc.date.issued.none.fl_str_mv 2011
dc.date.accessioned.none.fl_str_mv 2017-04-27T18:49:04Z
2022-07-07T01:37:20Z
dc.date.available.none.fl_str_mv 2017-04-27T18:49:04Z
2022-07-07T01:37:20Z
dc.type.none.fl_str_mv Articulo
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.eissn.none.fl_str_mv 0
dc.identifier.folio.none.fl_str_mv D07I1086
D07I1086
dc.identifier.idwos.none.fl_str_mv WOS:000293797600014
dc.identifier.isi.none.fl_str_mv WOS:000293797600014
dc.identifier.issn.none.fl_str_mv 0022-3042
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/196781
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url https://hdl.handle.net/10533/196781
dc.language.*.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.doi.none.fl_str_mv 10.1111/j.1471-4159.2011.07210.x
dc.relation.projectid.none.fl_str_mv info:eu-repo/grantAgreement/Fondef/D07I1086
dc.relation.set.none.fl_str_mv info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477
dc.relation.uri.none.fl_str_mv https://doi.org/10.1111/j.1471-4159.2011.07210.x
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.coverage.spatial.none.fl_str_mv MALDEN
dc.publisher.none.fl_str_mv WILEY-BLACKWELL
publisher.none.fl_str_mv WILEY-BLACKWELL
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
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spelling ORELLANA, JUANNAUS, CHRISTIANJIANG, JEANGIAUME, CHRISTIANEZAN, PASCALBENNET, MICHAELSAEZ-CARREÑO, JUAN201110.1111/j.1471-4159.2011.07210.xhttps://hdl.handle.net/10533/196781http://purl.org/coar/access_right/c_abf2Atp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels840826GBRMALDENSAEZ-CARREÑO, JUANBENNET, MICHAELEZAN, PASCALGIAUME, CHRISTIANJIANG, JEANNAUS, CHRISTIANORELLANA, JUAN2017-04-27T18:49:04Z2022-07-07T01:37:20Z2017-04-27T18:49:04Z2022-07-07T01:37:20Z2011Inflammation contributes to neurodegeneration in post-ischemic brain, diabetes, and Alzheimer's disease. Participants in this inflammatory response include activation of microglia and astrocytes. We studied the role of microglia treated with amyloid-beta peptide (A beta) on hemichannel activity of astrocytes subjected to hypoxia in high glucose. Reoxygenation after 3 h hypoxia in high glucose induced transient astroglial permeabilization via Cx43 hemichannels and reduction in intercellular communication via Cx43 cell-cell channels. Both responses were greater and longer lasting in astrocytes previously exposed for 24 h to conditioned medium from A beta-treated microglia (CM-A beta). The effects of CM-A beta were mimicked by TNF-alpha and IL-1 beta and were abrogated by neutralizing TNF-alpha with soluble receptor and IL-1 beta with a receptor antagonist. Astrocytes under basal conditions protected neurons against hypoxia, but exposure to CM-A beta made them toxic to neurons subjected to a sub-lethal hypoxia/reoxygenation episode, revealing the additive nature of the insults. Astrocytes exposed to CM-A beta induced permeabilization of cortical neurons through activation of neuronal pannexin 1 (Panx1) hemichannels by ATP and glutamate released through astroglial Cx43 hemichannels. In agreement, inhibition of NMDA or P2X receptors only partially reduced the activation of neuronal Panx1 hemichannels and neuronal mortality, but simultaneous inhibition of both receptors completely prevented the neurotoxic response. Therefore, we suggest that responses to ATP and glutamate converge in activation of neuronal Panx1 hemichannels. Thus, we propose that blocking hemichannels expressed by astrocytes and/or neurons in the inflamed nervous system could represent a novel and alternative strategy to reduce neuronal loss in various pathological states including Alzheimer's disease, diabetes and ischemia.This work was partially supported by the CRPCEN and INSERM (France; to CG); CONICYT 24080055 (to JAO); FONDECYT 1070591 (to JCS); FONDEF DO7I1086 (to JCS); ANILLO ACT-71 (to JCS), NIH (NS55363 to MVLB), INSERM (France; Departement des Relations Internationales to JAO), NIH AR46798 and Welch Foundation grant AQ-1507 (to JXJ) and the Heart & Stroke Foundation of BC & Yukon (CCN). Conception and design were performed by JAO, CG and JCS and most acquisition of data was performed by JAO. Moreover part of acquisition of data and analysis of data were performed by NF and PE. All authors contributed in equal form on interpretation of data, drafting the article and revising critically in it intellectual content. All authors declare no conflict of interest. The data of this work were presented by Dr Juan A. Orellana as partial fulfillment of the requirements to obtain the degree of PhD in Physiological Sciences at the Pontificia Universidad Catolica de Chile.98FONDEFjaorella@uc.clCRPCEN; INSERM (France); CONICYT [24080055]; FONDECYT [1070591]; FONDEF [DO7I1086]; ANILLO [ACT-71]; NIH [NS55363, AR46798]; INSERM (France; Departement des Relations Internationales); Welch Foundation [Q-1507]; Heart & Stroke Foundation of BC Yukon5FONDEF1180D07I1086D07I1086virtual::45066-1WOS:000293797600014WOS:0002937976000140022-3042https://hdl.handle.net/10533/196781WILEY-BLACKWELLinstname: Conicytreponame: Repositorio Digital RI2.0instname: Conicytreponame: Repositorio Digital RI2.010.1111/j.1471-4159.2011.07210.xinfo:eu-repo/grantAgreement/Fondef/D07I1086info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477https://doi.org/10.1111/j.1471-4159.2011.07210.xinfo:eu-repo/semantics/openAccessAtp and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannelsJOURNAL OF NEUROCHEMISTRYJ. Neurochem.Articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionengArticulohttps://hdl.handle.net/10533/196781FONDEFhttp://purl.org/coar/resource_type/c_2df8fbb1db41e1be-ddc8-49a6-82fc-ac8c925a39b7virtual::45066-1db41e1be-ddc8-49a6-82fc-ac8c925a39b7virtual::45066-110533/196781oai:repositorio.anid.cl:10533/1967812023-07-24 17:53:24.202https://repositorio.anid.clRepositorio ANIDaletelier@anid.cl
score 15.812429

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