NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth
| Autor: | Kazumi Iwata, Chihiro Yabe-Nishimura, Masato Katsuyama, ChunYuan Fan, Takahiko Yokoyama, Toru Nishinaka, Masakazu Ibi |
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| Rok vydání: | 2006 |
| Předmět: |
Neurite
Immunoblotting Tropomyosin receptor kinase A PC12 Cells Biochemistry Mice chemistry.chemical_compound Superoxides Physiology (medical) Nerve Growth Factor Neurites Animals RNA Messenger Enzyme Inhibitors Neurons chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology Reverse Transcriptase Polymerase Chain Reaction Superoxide NADPH Oxidases NOX4 Cell Differentiation Free Radical Scavengers Flow Cytometry Molecular biology Rats Isoenzymes Nerve growth factor nervous system chemistry NOX1 cardiovascular system biology.protein |
| Zdroj: | Free Radical Biology and Medicine. 40:1785-1795 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2006.01.009 |
| Popis: | Reactive oxygen species produced by NADPH oxidase are involved in the neuronal death associated with various neurodegenerative disorders. However, the role of NADPH oxidase in neuronal differentiation has not been well characterized. In nondifferentiated PC12 cells, the mRNA level of NOX1, a catalytic subunit of NADPH oxidase expressed in nonphagocytes, was approximately 10 times higher than that of the phagocyte type subunit, NOX2 (gp91(phox)), while the transcript of another isoform, NOX4, was not detected. Following nerve growth factor (NGF)-induced neurite outgrowth, the mRNA level of NOX1 and NOX2 was progressively increased and decreased, respectively. The NGF-induced increase in NOX1 mRNA was mediated by TrkA and accompanied by increased intracellular superoxide, which was suppressed by NADPH oxidase inhibitors. Unexpectedly, these inhibitors and superoxide scavengers significantly enhanced NGF-induced neurite outgrowth. Enhanced neurite outgrowth was similarly demonstrated in cells depleted with the NOX1 transcript by stable expression of ribozymes targeted for the NOX1 mRNA sequence. Furthermore, NGF-induced expression of betaIII-tubulin was significantly augmented in cells treated with NADPH oxidase inhibitors or stably expressing ribozymes. Phosphatidylinositol-3 (PI3) kinase inhibitors, without affecting NGF-induced NOX1 expression, augmented NGF-induced neurite outgrowth but not in clones expressing ribozymes. Taken together, increased superoxide production by up-regulation of NOX1 may negatively regulate neuronal differentiation by suppressing excessive neurite outgrowth. |
| Databáze: | OpenAIRE |
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