2004 Fiscal Year Final Research Report Summary
The analysis of onset of familial amyotrophic lateral sclerosis(FALS) with His46Arg point mutation
| Project/Area Number |
15590899
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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 | University of Miyazaki (2004)
宮崎医科大学 (2003) |
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Principal Investigator |
YAMAGUCHI Tadatoshi University of Miyazaki, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80037598)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Hajime University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助手 (80253839)
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| Project Period (FY) |
2003 – 2004
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| Keywords | dihydropyrazine / PC12 / Schwann cell / radical / Copper(II) |
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| Research Abstract |
The correlation between neurological disorders and dehydropyrazines(DHPs) that sugar-derived product having the activity of DNA fragmentation was examined. The damage of SOD function bring the existence of many free copper ion, and the effects of DHPs were accelerated in the cells in anterior horn of spinal cord of FALS patient with His46Arg point mutation, thus cells in central nerve seemed to be impaired. To demonstrate this hypothesis, the affect on the cellular functions of DHPs was analyzed using nerve cell lines.
The fluctuation of functional molecules in neural cell ; PC12 and Schwann cell, was assayed. Among three DHPs with different DNA fragmentation activity, DHP with the highest fragmentation activity (Yl-3) markedly affect the cellular function. The expression of structural proteins in the cells was almost unchanged, but beta-catenin expression was decreased in Schwann cells treated wjth Yl-3. Though the morphological changes by the addition of DHPs might indicate apoptosis
… More
occurred, the fragmentation of apoptosis marker molecule PARP was not detected.
The cellular effect was not detected in the presence of low density of DHP and copper ion, independently. MAPK molecules (ERK1/2,JNK, and p38) activate in Schwann cells with coexistence of DHP and copper ion. This suggested that low density DHP could degenerate neural cells with the presence of copper ion in vivo. Among cell cycle regulation systems, the expression of p27 and p16 was decreased and cdc2 protein was inactivated. The cell cycle of DHP-treated cells might indicate the convergence into the G1/S state, and it postulated that mitosis process was inhibited.
These results suggested that DHPs influenced MAPK activities with the presence of copper ion, and elevated the probability of onset of neurological disorder.
On the other hand, the reaction of DHPs with Cu2+ demonstrated that the presence of Cu2+ accelerated the effect of DHPs in the reaction system. A part of the results already was in press (Biol.Pharm.Bull.,2005), and other was submitted and then be under examination. Less
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Research Products
(1 results)
