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Título: | Differential contribution of the guanylyl cyclase-cyclic GMP-protein kinase G pathway to the proliferation of neural stem cells stimulated by nitric oxide | Autor: | Carreira, Bruno P. Morte, Maria Inês Lourenço, Ana Sofia Santos, Ana Isabel Inácio, Ângela Ambrósio, A. Francisco Carvalho, Caetana M. Araújo, Inês M. |
Palavras-chave: | Nitric oxide; Neural stem cells; cyclic GMP; cGMP-dependent kinase; Proliferation; Neurogenesis; Guanylyl cyclase | Data: | 2013 | Editora: | Karger | Projeto: | Calouste Gulbenkian Foundation, L’Oréal, UNESCO, and the Foundation for Science and Technology (FCT, Portugal), COMPETE and FEDER (project PTDC/SAU-NEU/102612/2008). SFRH/BPD/78901/2011 SFRH/BD/23754/2005 SFRH/ BD/38127/2007 |
Título da revista, periódico, livro ou evento: | NeuroSignals | Volume: | 21 | Número: | 1-2 | Resumo: | Nitric oxide (NO) is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP) and the cGMP-dependent kinase (PKG) are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ) were used. We observed that long-term exposure to the NO donor (24 h), NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h) increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner. | URI: | https://hdl.handle.net/10316/109755 | ISSN: | 1424-8638 1424-862X |
DOI: | 10.1159/000332811 | Direitos: | openAccess |
Aparece nas coleções: | I&D IBILI - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide.pdf | 1.16 MB | Adobe PDF | Ver/Abrir |
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