| Project/Area Number |
11558092
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
GETOH Yukiko Institute of Molecular and Cellular Biosciences, The University of Tokyo Associate professor, 分子細胞生物学研究所, 助教授 (70252525)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHIMA Yoshiyuki New Product Research Research Fellow Laboratories III, Daiichi, Pharmaceutical Co., Ltd., 創薬第三研究所, 研究員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1999: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | JNK / caspase / apoptosis / MAPキナーゼ / 細胞生存 / p38 / MST1 / PI3キナーゼ |
|---|
| Research Abstract |
The in vitro survival of cerebellar granule cells can be supported by a number of factors, including insulin like growth factor-I (IGF-1), forskolin and depolarizing concentrations of KCI.IGF-I-induced survival is mediated by the P13K-Akt pathway, whereas forskolin-induced survival is mediated by the cAMP- protein kinase A (PKA) pathway. However, the mechanisms by which these transduction pathways promote survival are not completely understood. We found that cerebellar granule cells from caspase-9 knockout mice were resistant to death induced by growth factor withdrawal, and to death induced by blockade of P13K activity or PKA activity. These results suggest that the P13K-Akt pathway and the cAMP-PKA pathway promote survival through the inhibition of caspase-9 either directly or indirectly. Interestingly, Akt and PKA phosphorylated caspase-9 in vitro and inhibited its activation. In addition, apoptosis induced by expression of caspase-9 was inhibited by co-expression of either active Akt or PKA.Taken together, these results suggest that caspase-9 is a direct target for Akt and PKA and thus serve to integrate multiple survival pathways.
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