The role of ubiquitin in neuronal apoptosis
| Project/Area Number |
09470290
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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 |
Cerebral neurosurgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KIRINO Takaaki Department of Neurosurgery, University of Tokyo Hospital Professor, 医学部・附属病院, 教授 (90126045)
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| Co-Investigator(Kenkyū-buntansha) |
UEKI Keisuke Department of Neurosurgery, University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (20302705)
IDE Takafumi Department of Neurosurgery, University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (40262000)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1997: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | ubiquitin / apoptosis / cell death / neuron / cerebral ischemia / hippocampus / delayed neuronal death / proteolysis / ラジオイムノアッセイ / ELISA / in situ hybridization |
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| Research Abstract |
Ubiquitin content was measured in the gerbil hippocampus following brief cerebral ischemia. Free and conjugated ubiquitin of the CA1 sector and CA3/dendate region are quantitated by radio-immunoassay or ELISA.The result was parallel with our former result by immunostaining. Following transient ischemia, free ubiquitin decreased in CA1 and it never recovered, whereas free ubiquitin transiently decreased in CA3/dentate region and then recovered to the control level within 48 hours. The content of conjugated ubiquitin remarkably increased in both of the regions. It decreased down to the normal level in CA3/dentate region but it maintained a high level at 48 hours following ischemia in CA1. In situ hybridization of ubiquitin mRNA demonstrated a marked increase of signal in the whole area of the hippocampus. Since free ubiquitin never recovered in CA1, translation of ubiquitin mRNA was blocked in this region. On the other hand, ubiquitin mRNA is translated and free ubiquitin rapidly recovered in tolerance-induced hippocampus. Decrease in free ubiquitin results in disturbance of ubiquitin-proteasome proteolytic system. We examined whether the disturbance of ubiquitin-proteasome system is a simple result of cell death process or it is an active process that could contribute to cell degradation. Proteasome activity was inhibited by proteasome inhibitor in cultured rat cortical neurons. The procedure resulted in caspase-3 activation and subsequent neuronal apoptosis. These results indicated that ubiquitin and proteasome are deeply and actively related in the process of delayed neuronal death in the hippocampus.
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Report
(3 results)
Research Products
(23 results)
