Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/21942 |
Resumo: | © 2016. Published by The Company of Biologists Ltd. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in miceApoptosisBrainCarbon monoxideCo-culturesPurinergicPreconditioning© 2016. Published by The Company of Biologists Ltd.The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNQueiroga, Cláudia S FAlves, Raquel M AConde, Sílvia VAlves, Paula MVieira, Helena L A2017-07-13T22:01:16Z2016-08-152016-08-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/21942eng0021-9533PURE: 1755286https://doi.org/10.1242/jcs.187260info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:09:06Zoai:run.unl.pt:10362/21942Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:27:03.237223Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
title |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
spellingShingle |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice Queiroga, Cláudia S F Apoptosis Brain Carbon monoxide Co-cultures Purinergic Preconditioning |
title_short |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
title_full |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
title_fullStr |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
title_full_unstemmed |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
title_sort |
Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice |
author |
Queiroga, Cláudia S F |
author_facet |
Queiroga, Cláudia S F Alves, Raquel M A Conde, Sílvia V Alves, Paula M Vieira, Helena L A |
author_role |
author |
author2 |
Alves, Raquel M A Conde, Sílvia V Alves, Paula M Vieira, Helena L A |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Centro de Estudos de Doenças Crónicas (CEDOC) NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Queiroga, Cláudia S F Alves, Raquel M A Conde, Sílvia V Alves, Paula M Vieira, Helena L A |
dc.subject.por.fl_str_mv |
Apoptosis Brain Carbon monoxide Co-cultures Purinergic Preconditioning |
topic |
Apoptosis Brain Carbon monoxide Co-cultures Purinergic Preconditioning |
description |
© 2016. Published by The Company of Biologists Ltd. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-08-15 2016-08-15T00:00:00Z 2017-07-13T22:01:16Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/21942 |
url |
http://hdl.handle.net/10362/21942 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0021-9533 PURE: 1755286 https://doi.org/10.1242/jcs.187260 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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|
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1799137899842633728 |