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

In English

Författare

  • Bruno Pereira Carreira
  • Maria Ines Morte
  • Angela Inacio
  • Gabriel Costa
  • Joana Rosmaninho-Salgado
  • Fabienne Agasse
  • Analia Carmo
  • Patricia Couceiro
  • Patrik Brundin
  • Antonio Francisco Ambrosio
  • Caetana Monteiro Carvalho
  • Ines Maria Araujo
Visa allt

Summary, in English

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

Publiceringsår

2010

Språk

Engelska

Sidor

1219-1230

Publikation/Tidskrift/Serie

Stem Cells

Volym

28

Issue

7

Dokumenttyp

Artikel i tidskrift

Förlag

AlphaMed Press

Ämne

  • Cell and Molecular Biology

Nyckelord

  • factor receptor
  • Epidermal growth
  • Cell proliferation
  • Nitric oxide
  • Neural stem cells

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1549-4918