Disclosing CO-induced cytoprotection in astrocytes: role of FosB
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/21595 |
Resumo: | Cerebral ischemia is a serious health problem, causing disability and death worldwide. Therefore, it is essential to develop strategies to protect and repair the brain. Recently, some studies on preconditioning started to emerge, where a toxic stimulus below the threshold of injury is given, inducing tolerance, preparing and strengthening the brain for a potential greater injury. In this project, it will be used carbon monoxide (CO) as a preconditioning agent, since its administration is able to produce several beneficial effects, namely acting as an anti-apoptotic and anti-inflammatory agent. The purpose of this work is to disclose CO-induced cytoprotection and the potential role of FosB associated to it. The experiments were developed using primary cultures of astrocytes isolated from newborn mice. As CO source the CO-releasing molecule CORM-A1 was used. CORM-A1 showed the ability to induce FosB protein expression in astrocytes, which was analyzed by western blot. However, it is not know yet how this increase is mediated. Reactive oxygen species (ROS) signaling is involved in CO and in FosB related pathways. Consequently, astrocytes were pre-treated with antioxidants (β-carotene or N-acetylcysteine) for decreasing cellular ROS levels. In addition P2X7 receptor also appears to be associated with FosB activation. Thus, P2X7 inhibitor (A-438079) was added to astrocytic culture in order to assess if FosB increased expression could be mediated by P2X7 receptor. Nevertheless, inhibition of ROS signaling did not change CO-induced FosB levels, while prevention of P2X7 activation showed a slight tendency to revert FosB expression, indicating that this pathway is independent on ROS but it could be mediated by P2X7 receptor. Although it is still a long way to go, these results gave more insight about CO-induced FosB activation, which is important for understanding the molecular mechanisms underlying CO-induced cytoprotection. Potential therapeutic applications of CO will depend on a clear understanding of its pathways and would potentially allow the development of more efficient therapies against cerebral ischemia. |
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Disclosing CO-induced cytoprotection in astrocytes: role of FosBCarbon monoxideCORM-A1PreconditioningFosBReactive oxygen speciesP2X7 receptorDomínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e TecnologiasCerebral ischemia is a serious health problem, causing disability and death worldwide. Therefore, it is essential to develop strategies to protect and repair the brain. Recently, some studies on preconditioning started to emerge, where a toxic stimulus below the threshold of injury is given, inducing tolerance, preparing and strengthening the brain for a potential greater injury. In this project, it will be used carbon monoxide (CO) as a preconditioning agent, since its administration is able to produce several beneficial effects, namely acting as an anti-apoptotic and anti-inflammatory agent. The purpose of this work is to disclose CO-induced cytoprotection and the potential role of FosB associated to it. The experiments were developed using primary cultures of astrocytes isolated from newborn mice. As CO source the CO-releasing molecule CORM-A1 was used. CORM-A1 showed the ability to induce FosB protein expression in astrocytes, which was analyzed by western blot. However, it is not know yet how this increase is mediated. Reactive oxygen species (ROS) signaling is involved in CO and in FosB related pathways. Consequently, astrocytes were pre-treated with antioxidants (β-carotene or N-acetylcysteine) for decreasing cellular ROS levels. In addition P2X7 receptor also appears to be associated with FosB activation. Thus, P2X7 inhibitor (A-438079) was added to astrocytic culture in order to assess if FosB increased expression could be mediated by P2X7 receptor. Nevertheless, inhibition of ROS signaling did not change CO-induced FosB levels, while prevention of P2X7 activation showed a slight tendency to revert FosB expression, indicating that this pathway is independent on ROS but it could be mediated by P2X7 receptor. Although it is still a long way to go, these results gave more insight about CO-induced FosB activation, which is important for understanding the molecular mechanisms underlying CO-induced cytoprotection. Potential therapeutic applications of CO will depend on a clear understanding of its pathways and would potentially allow the development of more efficient therapies against cerebral ischemia.Vieira, HelenaRUNSilva, Deborah Soares Neto Zucolotto da2017-06-20T13:46:43Z2016-092017-062016-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/21595enginfo: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:RCAAP2024-03-11T04:08:24Zoai:run.unl.pt:10362/21595Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:52.522408Repositório 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 |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
title |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
spellingShingle |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB Silva, Deborah Soares Neto Zucolotto da Carbon monoxide CORM-A1 Preconditioning FosB Reactive oxygen species P2X7 receptor Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
title_short |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
title_full |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
title_fullStr |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
title_full_unstemmed |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
title_sort |
Disclosing CO-induced cytoprotection in astrocytes: role of FosB |
author |
Silva, Deborah Soares Neto Zucolotto da |
author_facet |
Silva, Deborah Soares Neto Zucolotto da |
author_role |
author |
dc.contributor.none.fl_str_mv |
Vieira, Helena RUN |
dc.contributor.author.fl_str_mv |
Silva, Deborah Soares Neto Zucolotto da |
dc.subject.por.fl_str_mv |
Carbon monoxide CORM-A1 Preconditioning FosB Reactive oxygen species P2X7 receptor Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
topic |
Carbon monoxide CORM-A1 Preconditioning FosB Reactive oxygen species P2X7 receptor Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
description |
Cerebral ischemia is a serious health problem, causing disability and death worldwide. Therefore, it is essential to develop strategies to protect and repair the brain. Recently, some studies on preconditioning started to emerge, where a toxic stimulus below the threshold of injury is given, inducing tolerance, preparing and strengthening the brain for a potential greater injury. In this project, it will be used carbon monoxide (CO) as a preconditioning agent, since its administration is able to produce several beneficial effects, namely acting as an anti-apoptotic and anti-inflammatory agent. The purpose of this work is to disclose CO-induced cytoprotection and the potential role of FosB associated to it. The experiments were developed using primary cultures of astrocytes isolated from newborn mice. As CO source the CO-releasing molecule CORM-A1 was used. CORM-A1 showed the ability to induce FosB protein expression in astrocytes, which was analyzed by western blot. However, it is not know yet how this increase is mediated. Reactive oxygen species (ROS) signaling is involved in CO and in FosB related pathways. Consequently, astrocytes were pre-treated with antioxidants (β-carotene or N-acetylcysteine) for decreasing cellular ROS levels. In addition P2X7 receptor also appears to be associated with FosB activation. Thus, P2X7 inhibitor (A-438079) was added to astrocytic culture in order to assess if FosB increased expression could be mediated by P2X7 receptor. Nevertheless, inhibition of ROS signaling did not change CO-induced FosB levels, while prevention of P2X7 activation showed a slight tendency to revert FosB expression, indicating that this pathway is independent on ROS but it could be mediated by P2X7 receptor. Although it is still a long way to go, these results gave more insight about CO-induced FosB activation, which is important for understanding the molecular mechanisms underlying CO-induced cytoprotection. Potential therapeutic applications of CO will depend on a clear understanding of its pathways and would potentially allow the development of more efficient therapies against cerebral ischemia. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-09 2016-09-01T00:00:00Z 2017-06-20T13:46:43Z 2017-06 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/21595 |
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http://hdl.handle.net/10362/21595 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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