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)

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 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
Volume275
Issue number18
DOIs
Publication statusPublished - 5 May 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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