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Nitric Oxide Stimulates the Proliferation of Neural Stem Cells Bypassing the Epidermal Growth Factor Receptor

Carreira, Bruno Pereira; Morte, Maria Ines; Inacio, Angela; Costa, Gabriel; Rosmaninho-Salgado, Joana; Agasse, Fabienne; Carmo, Analia; Couceiro, Patricia; Brundin, Patrik LU and Ambrosio, Antonio Francisco, et al. (2010) In Stem Cells 28(7). p.1219-1230
Abstract
Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 mu M) increased cell proliferation, whereas higher concentrations (100 mu M) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway,... (More)
Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 mu M) increased cell proliferation, whereas higher concentrations (100 mu M) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway, independently of the epidermal growth factor (EGF) receptor. Downstream of the EGF receptor, NO activated p21Ras and the MAPK pathway, resulting in a decrease in the nuclear presence of the cyclin-dependent kinase inhibitor I, p27(KIP1), allowing for cell cycle progression. Furthermore, in a mouse model that shows increased proliferation of neural stem cells in the hippocampus following seizure injury, we observed that the absence of inducible nitric oxide synthase (iNOS(-/-) mice) prevented the increase in cell proliferation observed following seizures in wild-type mice, showing that NO from iNOS origin is important for increased cell proliferation following a brain insult. Overall, we show that NO is able to stimulate the proliferation of neural stem cells bypassing the EGF receptor and promoting cell division. Moreover, under pathophysiological conditions in vivo, NO from iNOS origin also promotes proliferation in the hippocampus. STEM CELLS 2010:28:1219-1230 (Less)
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publication status
published
subject
keywords
factor receptor, Epidermal growth, Cell proliferation, Nitric oxide, Neural stem cells
in
Stem Cells
volume
28
issue
7
pages
1219 - 1230
publisher
AlphaMed Press
external identifiers
  • wos:000280746400011
  • scopus:77954821915
ISSN
1549-4918
DOI
10.1002/stem.444
language
English
LU publication?
yes
id
9a052256-4a03-48e6-a7bc-caaea93b8e70 (old id 1674066)
date added to LUP
2010-09-22 14:01:27
date last changed
2018-05-29 09:36:50
@article{9a052256-4a03-48e6-a7bc-caaea93b8e70,
  abstract     = {Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 mu M) increased cell proliferation, whereas higher concentrations (100 mu M) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway, independently of the epidermal growth factor (EGF) receptor. Downstream of the EGF receptor, NO activated p21Ras and the MAPK pathway, resulting in a decrease in the nuclear presence of the cyclin-dependent kinase inhibitor I, p27(KIP1), allowing for cell cycle progression. Furthermore, in a mouse model that shows increased proliferation of neural stem cells in the hippocampus following seizure injury, we observed that the absence of inducible nitric oxide synthase (iNOS(-/-) mice) prevented the increase in cell proliferation observed following seizures in wild-type mice, showing that NO from iNOS origin is important for increased cell proliferation following a brain insult. Overall, we show that NO is able to stimulate the proliferation of neural stem cells bypassing the EGF receptor and promoting cell division. Moreover, under pathophysiological conditions in vivo, NO from iNOS origin also promotes proliferation in the hippocampus. STEM CELLS 2010:28:1219-1230},
  author       = {Carreira, Bruno Pereira and Morte, Maria Ines and Inacio, Angela and Costa, Gabriel and Rosmaninho-Salgado, Joana and Agasse, Fabienne and Carmo, Analia and Couceiro, Patricia and Brundin, Patrik and Ambrosio, Antonio Francisco and Carvalho, Caetana Monteiro and Araujo, Ines Maria},
  issn         = {1549-4918},
  keyword      = {factor receptor,Epidermal growth,Cell proliferation,Nitric oxide,Neural stem cells},
  language     = {eng},
  number       = {7},
  pages        = {1219--1230},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Nitric Oxide Stimulates the Proliferation of Neural Stem Cells Bypassing the Epidermal Growth Factor Receptor},
  url          = {http://dx.doi.org/10.1002/stem.444},
  volume       = {28},
  year         = {2010},
}