2015 Fiscal Year Final Research Report
Mechanisms of regulation and signaling of NADPH oxidase 1 involved in cell proliferation
| Project/Area Number |
24510299
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Ehime University |
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Principal Investigator |
Tamura Minoru 愛媛大学, 理工学研究科, 准教授 (00128349)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | superoxide / Nox1 / betaPix / phosphorylation / colon epithelial cells / signaling |
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| Outline of Final Research Achievements |
Nox1 produces superoxide (O2-) in response to growth hormone such as EGF in colon epithelial cells. We found that betaPix is involved in the activation of Nox1, and EGF-induced phosphorylation at Ser-340 of betaPix enhanced its Nox1-activating ability. The phosphomimetic mutant of betaPix showed higher Rac-binding and GDP/GTP exchange ability which is required for Nox1 activation. In contrast, phosphorylation at Ser-525 eliminated its ability of Nox1 activation. Based on the results of in vivo and in vitro experiments with the phosphomimetic, unphosphorylatable, and truncated mutants, we proposed a mechanism of how phosphorylations at different sites caused opposite effects on Nox1-activating ability of betaPix.
We also examined the effect of O2- on Caco-2 cells using an O2- generating device we have developed, and found that O2- exogenously added caused apoptosis in the cells, and also oxidation of several cytosolic proteins involved in cytoskeleton, glycolysis, and protein synthesis.
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| Free Research Field |
生化学, 細胞生物学
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