S-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model

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dc.contributor.authorSantos, Ana Isabel
dc.contributor.authorPereira Carreira, Bruno
dc.contributor.authorIzquierdo-Álvarez, Alicia
dc.contributor.authorRamos, Elena
dc.contributor.authorLourenço, Ana Sofia
dc.contributor.authorSantos, Daniela Filipa
dc.contributor.authorMorte, Maria Inês
dc.contributor.authorRibeiro, Luís Filipe
dc.contributor.authorMarreiros, Ana
dc.contributor.authorSánchez-López, Nuria
dc.contributor.authorMarina, Anabel
dc.contributor.authorMonteiro Carvalho, Caetana
dc.contributor.authorMartínez Ruiz, Antonio
dc.contributor.authorAraújo, Inês Maria
dc.date.accessioned2024-04-10T08:24:30Z
dc.date.available2024-04-10T08:24:30Z
dc.date.issued2018-01
dc.description.abstractAims: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, downstream of the epidermal growth factor receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed at studying the possible neurogenic action of NO by posttranslational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSCs). Results: We show that NO caused S-nitrosylation (SNO) of p21Ras in Cys118, which triggered downstream activation of the ERK/MAPK pathway and proliferation of NSC. Moreover, in cells overexpressing a mutant Ras in which Cys118 was replaced by a serine–C118S–, cells were insensitive to NO, and no increase in SNO, in ERK phosphorylation, or in cell proliferation was observed. We also show that, after seizures, in the presence of NO derived from inducible nitric oxide synthase, there was an increase in p21Ras cysteine modification that was concomitant with the previously described stimulation of proliferation in the dentate gyrus. Innovation: Our work identifies p21Ras and its SNO as an early target of NO during signaling events that lead to NSC proliferation and neurogenesis. Conclusion: Our data highlight Ras SNO as an early event leading to NSC proliferation, and they may provide a target for NO-induced stimulation of neurogenesis with implications for brain repair
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipFoundation for Science and Technology
dc.description.sponsorshipISCIII, Spanish Government, partially funded by FEDER/ EDRF
dc.description.statuspub
dc.identifier.doi10.1089/ars.2016.6858
dc.identifier.issn1523-0864
dc.identifier.issn1557-7716
dc.identifier.officialurlhttps://www.liebertpub.com/doi/abs/10.1089/ars.2016.6858?journalCode=ars
dc.identifier.urihttps://hdl.handle.net/20.500.14352/102924
dc.issue.number1
dc.journal.titleAntioxidants & Redox Signaling
dc.language.isoeng
dc.page.final30
dc.page.initial15
dc.relation.projectIDSFRH/BD/77903/ 2011
dc.relation.projectIDSFRH/BD/79308/2011
dc.relation.projectIDPTDC/NEU-OSD/0473/2012
dc.relation.projectIDUID/BIM/04773/2013
dc.relation.projectIDUID/NEU/04539/2013
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN//PS09%2F00101/ES/PAPEL DE LAS ESPECIES REACTIVAS DE OXIGENO Y NITROGENO Y DE LAS MODIFICACIONES OXIDATIVAS DE PROTEINAS EN LA RESPUESTA A HIPOXIA EN FISIOPATOLOGIA CARDIOVASCULAR/
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//PI12%2F00875/ES/Modificaciones postraduccionales oxidativas en fisiopatología molecular/
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//PI15%2F00107/ES/Señalización en hipoxia por especies reactivas de oxígeno, y proteómica redox: de los mecanismos moleculares a las aplicaciones clínicas/
dc.relation.projectIDRI-AIBPT-2011-1015/ E-10/12
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//PT13%2F0001%2F0024/ES/Plataforma de recursos biomoleculares y bioinformaticos/
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.1
dc.subject.keywordNitric oxide
dc.subject.keywordNeural stem cells
dc.subject.keywordNeurogenesis
dc.subject.keywordp21Ras
dc.subject.keywordS-nitrosylation
dc.subject.ucmBioquímica (Farmacia)
dc.subject.unesco2302 Bioquímica
dc.titleS-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number28
dspace.entity.typePublication
relation.isAuthorOfPublicationeec0b303-34c9-47dd-9ec6-704b6c6c7acd
relation.isAuthorOfPublication.latestForDiscoveryeec0b303-34c9-47dd-9ec6-704b6c6c7acd
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