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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

dc.contributor.authorCarreira, Bruno P.
dc.contributor.authorMorte, Maria Inêss
dc.contributor.authorLourenço, Ana Sofia
dc.contributor.authorSantos, Ana Isabel
dc.contributor.authorInácio, Ângela
dc.contributor.authorAmbrósio, António F.
dc.contributor.authorCarvalho, Caetana M.
dc.contributor.authorAraújo, Inês
dc.date.accessioned2018-12-07T14:52:57Z
dc.date.available2018-12-07T14:52:57Z
dc.date.issued2013-02
dc.description.abstractNitric 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. Copyright (C) 2012 S. Karger AG, Basel
dc.description.sponsorshipCalouste Gulbenkian Foundation; L'Oreal; UNESCO; Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/78901/2011, SFRH/BD/23754/2005, SFRH/BD/38127/2007]; COMPETE; FEDER [PTDC/SAU-NEU/102612/2008]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1159/000332811
dc.identifier.issn1424-862X
dc.identifier.issn1424-8638
dc.identifier.urihttp://hdl.handle.net/10400.1/11284
dc.language.isoeng
dc.peerreviewedyes
dc.publisherKarger
dc.relationPHYSIOLOGICAL ROLE OF CALPAINS: HOW DO CALPAINS REGULATE CELL PROLIFERATION AND MIGRATION IN THE BRAIN
dc.relationEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectFocal cerebral ischemia
dc.subjectMouse subventricular zone
dc.subjectGrowth factor receptor
dc.subjectAdult brain
dc.subjectFunctional recovery
dc.subjectDentate gyrus
dc.subjectRat brain
dc.subjectNeurogenesis
dc.subjectStroke
dc.subjectInflammation
dc.titleDifferential contribution of the guanylyl cyclase-cyclic GMP-protein kinase g pathway to the proliferation of neural stem cells stimulated by nitric oxide
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePHYSIOLOGICAL ROLE OF CALPAINS: HOW DO CALPAINS REGULATE CELL PROLIFERATION AND MIGRATION IN THE BRAIN
oaire.awardTitleEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F78901%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F23754%2F2005/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F38127%2F2007/PT
oaire.citation.endPage13
oaire.citation.issue01-fev
oaire.citation.startPage1
oaire.citation.titleNeurosignals
oaire.citation.volume21
oaire.fundingStreamSFRH
person.familyNamePombinho de Araújo
person.givenNameInês Maria
person.identifierF-4703-2012
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id56271084100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication.latestForDiscovery1d0c21f4-0f4b-4589-8412-fe1079419774
relation.isProjectOfPublication12ca8423-71fc-4b29-992a-927c93b76261
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