Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109426
Title: Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling
Authors: Carreira, Bruno P. 
Morte, Maria I. 
Santos, Ana I. 
Lourenço, Ana Sofia 
Ambrósio, A. Francisco 
Carvalho, Caetana M. 
Araújo, Inês M. 
Keywords: inflammation; microglia; nitricoxide; neuralstemcells; cellproliferation
Issue Date: 2014
Publisher: Frontiers Media S.A.
Project: This workwassupportedbytheFoundationforScienceand Technology,(FCT,Portugal),COMPETEandFEDER(grants PEst-C/SAU/LA0001/2013-2014,PEst-OE/EQB/LA0023/2013- 2014,PTDC/SAU-NEU/102612/2008andPTDC/NEU-OSD/0473/ 2012). BrunoP.Carreira,MariaI.Morte,AnaI.Santos, and AnaS.LourençoweresupportedbyFCT,Portu- gal (fellowshipsSFRH/BPD/78901/2011,SFRH/BD/38127/2007, SFRH/BD/77903/2011, andSFRH/BD/79308/2011) 
Serial title, monograph or event: Frontiers in Cellular Neuroscience
Volume: 8
Issue: October
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.
URI: https://hdl.handle.net/10316/109426
ISSN: 1662-5102
DOI: 10.3389/fncel.2014.00343
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

Show full item record

Page view(s)

55
checked on May 29, 2024

Download(s)

15
checked on May 29, 2024

Google ScholarTM

Check

Altmetric

Altmetric


This item is licensed under a Creative Commons License Creative Commons