Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109426
DC Field | Value | Language |
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dc.contributor.author | Carreira, Bruno P. | - |
dc.contributor.author | Morte, Maria I. | - |
dc.contributor.author | Santos, Ana I. | - |
dc.contributor.author | Lourenço, Ana Sofia | - |
dc.contributor.author | Ambrósio, A. Francisco | - |
dc.contributor.author | Carvalho, Caetana M. | - |
dc.contributor.author | Araújo, Inês M. | - |
dc.date.accessioned | 2023-10-13T11:05:56Z | - |
dc.date.available | 2023-10-13T11:05:56Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1662-5102 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/109426 | - |
dc.description.abstract | Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-γ), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO(-)), or using the ONOO(-) degradation catalyst FeTMPyP, cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 μM), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway. | pt |
dc.description.sponsorship | This work was supported by the Foundation for Science and Technology,(FCT,Portugal),COMPETE and FEDER(grants PEst-C/SAU/LA0001/2013-2014,PEst-OE/EQB/LA0023/2013- 2014,PTDC/SAU-NEU/102612/2008 and PTDC/NEU-OSD/0473/ 2012). Bruno P.Carreira ,MariaI.Morte, AnaI.Santos, and Ana S.Lourenço supported ,Portugal (fellowships SFRH/BPD/78901/2011,SFRH/BD/38127/2007, SFRH/BD/77903/2011, and SFRH/BD/79308/2011) | pt |
dc.language.iso | eng | pt |
dc.publisher | Frontiers Media S.A. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | inflammation | pt |
dc.subject | microglia | pt |
dc.subject | nitricoxide | pt |
dc.subject | neuralstemcells | pt |
dc.subject | cellproliferation | pt |
dc.title | Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling | pt |
dc.type | article | - |
degois.publication.firstPage | 343 | pt |
degois.publication.issue | October | pt |
degois.publication.title | Frontiers in Cellular Neuroscience | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3389/fncel.2014.00343 | pt |
degois.publication.volume | 8 | pt |
dc.date.embargo | 2014-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | article | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.cerifentitytype | Publications | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-7874-6545 | - |
crisitem.author.orcid | 0000-0002-0477-1641 | - |
Appears in Collections: | I&D IBILI - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling.pdf | 2.17 MB | Adobe PDF | View/Open |
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