| Project/Area Number |
10480219
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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 | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Fukushima Medical University School of Medicine |
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Principal Investigator |
WANAKA Akio Fukushima Medical University, School of Medicine, Professor, 医学部, 教授 (90210989)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Tetsuji Fukushima Medical University, School of Medicine, Lecturer, 医学部, 助手 (30285043)
YOKOYA Sachihiko Fukushima Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (00045642)
清澤 秀孔 福島県立医科大学, 医学部, 助手 (30295422)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | Apoptosis / DP5 / Bcl-2 / BH3 domain / neuron / amyotrophic lateral sclerosis / 神経細胞 / 強制発現 / Yeast Two hybrid / Bcl-2 ファミリー / BH3 ドメイン / 脳虚血 |
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| Research Abstract |
We cloned a novel gene, whose expression was upregulated when cells undergo apoptosis, and named DP5. DP5 gene encoded a protein consisting of 92 amtino acids. DP5 protein had a BH3 (Bcl-2 homology domain 3) domain and had apoptosis-inducing activity when overexpressed in cultured neurons. These results suggested that DP5 was a novel proapoptotic member of the Bcl-2 family. We investigated distribution pattern of DP5 mRNA in the developing rat embryo by in situ hybridization and found that it was specifically expressed in the embryonic spinal motoneurons and autonomic ganglia. These tissues are known to prune superfluous neurons by apoptotic mechanism. Therefore, the DP5 gene might be involved in such apoptotic process. We also detected moderate DP5 mRNA expression in the postnatal hippocampus and cerebral cortex. We noted significant upregulation of the DP5 gene expression in the adult hippocampus aud cerebral cortex in response to ischemic insults, suggesting that DP5 is also involved in the ischemic neuronal death. Recent studies revealed an increasing number of BH3 only proteins such as Bik, Bim, and Blk. Among them, Bim specifically interacted with cytoskeletal component. This interaction regulated Bim's cell-death inducing activity ; detachment from cytoskeleton promoted Bim to relocate to mitochondrial membrane, and thereby induced apoptosis. Such a regulatory mechanisms may exist in the case of DP5. We searched for DP5-interacting molecule with yeast-two hybrid method. We have so far found three candidates, one of which is hn RNP.Possible regulatory mechanisms by these candidates are to be investigated in near future. Finally we investigated possible involvement of DP5 in degenerative neurological disease. We found that Harakiri (human homolog of DP5) was specifically expressed in the motoneurons of the amyotrophic lateral sclerosis patients.
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