| Project/Area Number |
15K10302
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurosurgery
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
篠山 隆司 神戸大学, 医学部附属病院, 講師 (10379399)
甲村 英二 神戸大学, 医学研究科, 教授 (30225388)
篠原 正和 神戸大学, 医学(系)研究科(研究院), 研究員 (80437483)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 脳虚血 / メタボロミクス / ペントースリン酸 / NADPH / cerebral ischemia / metabolomics / pentose phosphate / 脳代謝 / オミクス / ペントースリン酸経路 / 熱ショックタンパク / トランスクリプトミクス |
|---|
| Outline of Final Research Achievements |
We performed comparative metabolic analysis of reperfusion effect on cerebral metabolism using rat middle cerebral artery occlusion (MCAO). Gas-chromatography/mass-spectrometry analysis showed metabolic changes that depended on reperfusion time. Enrichment analysis showed pentose phosphate pathway (PPP) was significantly upregulated during ischemia-reperfusion. Immunoblotting showed gradual increase in HSP27 and marked increase in HSP27 phosphorylation. G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. ATM kinase inhibitor significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size after reperfusion. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant system during ischemia-reperfusion.
|
