Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species

Kazumi Suzukawa, Koichi Miura, Junji Mitsushita, James Resau, Kunitaka Hirose, Ronald Crystal, Tohru Kamata

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205 Citations (Scopus)


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 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.

Original languageEnglish
Pages (from-to)13175-13178
Number of pages4
JournalJournal of Biological Chemistry
Issue number18
Publication statusPublished - 5 May 2000
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry

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