Mechanisms of regulation and signaling of NADPH oxidase 1 involved in cell proliferation
| Project/Area Number |
24510299
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Living organism molecular science
|
|---|
| Research Institution | Ehime University |
|---|
Principal Investigator |
Tamura Minoru 愛媛大学, 理工学研究科, 准教授 (00128349)
|
|---|
| Project Period (FY) |
2012-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | superoxide / Nox1 / betaPix / phosphorylation / colon epithelial cells / signaling / signal transduction / oxidative stress / apoptosis / nanodevice / Caco-2 / beta Pix / NADPH oxidase / Noxa1 / Nox2 / Rac / p22phox / ROS |
|---|
| 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.
|
Report
(5 results)
Research Products
(21 results)
