| Project/Area Number |
20890025
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (Start-up)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Emergency medicine
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
OKADA Masashi Yamagata University, 医学部, 助教 (70512614)
|
|---|
| Project Period (FY) |
2008 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
|
|---|
| Keywords | 虚血 / 低酸素 / ユビキチン / DGK / リン脂質 / タンパク質分解 / 細胞死 / シグナル伝達 / ストレス / 神経細胞 / PC12 |
|---|
| Research Abstract |
In previous study, we demonstrated that diacylglycerol kinase (DGK)z which is distributed at nucleus in normal hippocampal neuron in vivo, is translocated to cytoplasm from nucleus by middle cerebral artery infarction in rat. But it is unclear that the mechanisms of ischemia induced translocation of DGKz and the physiological functions after localization in cytoplasm of DGKz. In this study, we demonstrated that DGKz nuclear export is regulated that calcium influx signaling after ischemia. Moreover, cytoplasmic DGKz is poly-ubiquitinated and degradated in hippocampal neuron in vitro and in vivo. This downregulation causes ER stress induced cell death following expression of cyclin D and cyclin E in neurons after ischema using DGKz deficient mice and siRNA knocdown study in vivo and in vitro. These datas suggest that DGKz is a downregulator of ischemic calcium signaling by inhibiting cyclin expression and cell cycle re-entry of neurons.
|
