| Project/Area Number |
17590897
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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 | Juntendo University |
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Principal Investigator |
URABE Takao Juntendo University, Neurology, Associate professor, 医学部, 助教授 (60291663)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Nobutaka Juntendo University, Neurology, Professor, 医学部, 教授 (80218510)
MIZUNO Yoshikuni Juntendo University, Neurology, Professor, 医学部, 教授 (30049043)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | RNA editing / Cerebral infarction / Mutant ubiquitin / Proteasome / Neuronal death / Neuroprotection |
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| Research Abstract |
Background and Purpose of this study
Accumulation of mutant ubiquitin-B (UBB^<+1>) produced by RNA editing in neurons is considered the hallmark of proteasomal dysfunction in neurodegenerative disorders, however no such evidence in ischemic brain has been reported. We investigated the contribution of UBB^<+1> in delayed neuronal death after transient global ischemia.
Serial changes in UBB^<+1> protein and transcripts in gerbil brain
We evaluated the expression of UBB^<+1> transcripts and protein in gerbil brain after transient global ischemia. To investigate the serial change and cellular localization of UBB^<+1> protein, we performed immunohistochemical study in a gerbil brain after transient global ischemia. In the CA1 region, UBB^<+1> immunoreactivity appeared in the cytoplasm of pyramidal cells at 30 min post-ischemia, and the density of these neurons increased at day 2 and further increased at day 4 post-ischemia. In contrast, UBB^<+1> immunoreactivity was only transiently detected f
… More
rom 30 min to 1 day post-ischemia in CA3, dentate gyrus, and frontal cortex, but disappeared at day 2 post-ischemia.
To investigate the serial change and cellular localization of UBB^<+1> mRNA, we performed RT-PCR study in a same model. UBB^<+1> mRNA was detected by RT-PCR in every region of the hippocampus and frontal cortex of ischemic gerbils and even in the non-ischemic control animals, and its expression level was independent of brain region and time after ischemia.
Our results indicate induction and selective accumulation of UBB^<+1> protein in dying neurons of the CA1 region and suggest that UBB^<+1> is a potential mediator of ubiquitin proteasomal dysfunction and may have an important role in modifying delayed neuronal death.
Evaluation of proteasomal function in vitro hypoxia model
To assess the relationship of proteasomal function for ischemic neuronal death, we performed immunochemical study for hypoxia-inducible factor-1 using hypoxic culture system of neurons or /and astrocytes. Less
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