| Project/Area Number |
21591081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
SASAKI Tsutomu 大阪大学, 医学部附属病院, 助教 (20534879)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Kazuo 大阪大学, 医学系・研究科, 准教授 (70301257)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | NMDA受容体 / NR2A / NR2B / TORC1/ CRTC1 / SIK2 / CREB / NDMA受容体 / サブタイプ / α7 nchR / 脳虚血 / TORC1 / NDMA受容 / 虚血耐性 |
|---|
| Research Abstract |
The cAMP responsive element-binding protein(CREB) functions in a broad array of biological and pathophysiological processes. We found that salt-inducible kinase 2(SIK2) was abundantly expressed in neurons and suppressed CREB-mediated gene expression after oxygen-glucose deprivation(OGD). OGD induced the degradation of SIK2 protein concomitantly with the dephosphorylation of the CREB-specific coactivator transducer of regulated CREB activity 1(TORC1), resulting in the activation of CREB and its downstream gene targets. Ca(2+)/ calmodulin-dependent protein kinase I/ IV are capable of phosphorylating SIK2 at Thr484, resulting in SIK2 degradation in cortical neurons. Neuronal survival after OGD was significantly increased in neurons isolated from sik2(-/-) mice, and ischemic neuronal injury was significantly reduced in the brains of sik2(-/-) mice subjected to transient focal ischemia. These findings suggest that SIK2 plays critical roles in neuronal survival, is modulated by CaMK I/ IV, and regulates CREB via TORC1.
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