Nerve Growth Factor-induced Neuronal Differentiation Requires Generation of Rac1-regulated Reactive Oxygen Species

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 PC1...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-05, Vol.275 (18), p.13175-13178
Main Authors: Suzukawa, Kazumi, Miura, Koichi, Mitsushita, Junji, Resau, James, Hirose, Kunitaka, Crystal, Ronald, Kamata, Tohru
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - drug effects
Cell Differentiation - physiology
flavoprotein-binding protein
Nerve Growth Factor - pharmacology
Neurons - cytology
Neurons - drug effects
Neurons - physiology
PC12 Cells
rac1 GTP-Binding Protein - physiology
Rac1 protein
Rats
Reactive Oxygen Species - physiology
Signal Transduction - drug effects
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Summary: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 byN-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 H2O2, 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 H2O2, 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.275.18.13175