Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Differentiation
  • PC12 Cells
  • Rats
  • Signal Transduction

MeSH Major

  • Nerve Growth Factor
  • Neurons
  • Reactive Oxygen Species
  • rac1 GTP-Binding Protein

abstract

  • Nerve growth factor (NGF) stimulation of pheochromocytoma PC12 cells transiently increased the intracellular concentration of reactive oxygen species (ROS). This increase was blocked by the chemical antioxidant N-acetylcysteine and a flavoprotein inhibitor, diphenylene iodonium. NGF responses of PC12 cells, including neurite outgrowth, tyrosine phosphorylation, and AP-1 activation, was inhibited when ROS production was prevented by N-acetylcysteine and diphenylene iodonium. The expression of dominant negative Rac1N17 blocked induction of both ROS generation and morphological differentiation by NGF. The ROS produced appears to be H(2)O(2), because the introduction of catalase into the cells abolished NGF-induced neurite outgrowth, ROS production, and tyrosine phosphorylation. These results suggest that the ROS, perhaps H(2)O(2), acts as an intracellular signal mediator for NGF-induced neuronal differentiation and that NGF-stimulated ROS production is regulated by Rac1 and a flavoprotein-binding protein similar to the phagocytic NADPH oxidase.

publication date

  • May 5, 2000

has subject area

  • Animals
  • Cell Differentiation
  • Nerve Growth Factor
  • Neurons
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species
  • Signal Transduction
  • rac1 GTP-Binding Protein

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 10788420

Additional Document Info

start page

  • 13175

end page

  • 13178

volume

  • 275

number

  • 18