| Project/Area Number | 07670738 |
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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 Nagoya |
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Principal Investigator |
YONEDA Makoto Nagoya University, Department of Biomedical Chemistry, Research Assistant, 医学部, 助手 (70270551)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Takayuki Nagoya University, Department of Biomedical Chemistry, Professor Emeritus, 医学部, 名誉教授 (80022771)
TANAKA Masashi Nagoya University, Department of Biomedical Chemistry, Associate Professor, 医学部, 助教授 (60155166)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed(Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1996 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1995 : ¥1,300,000 (Direct Cost : ¥1,300,000)
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| Keywords | mitochondrial genome / mitochondrial diseases / nucleotide substitutions / cell fusion / oxidative damage / cell death / reactive oxygen species / signal peptide / ミトコンドリア / ρ^0細胞 / 酸素ストレス / 活性酸素ラジカル / 遺伝子欠失 |
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| Research Abstract |
To gain an insight into the role of oxidative damages in the human diseases caused by mitochondrial DNA (mtDNA) mutations or during the physiological aging process, we have investigated the vulnerability to a high concentration of oxygen atmosphere (oxygen stress) and the oxidative damage to mtDNA in cultured cell lines carrying normal mtDNA (p^+), lacking mtDNA (p^0), or harboring mitochondrial tRNA gene mutations (syn^-) which are responsible for human neuromuscular disorders : mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) or myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome. These syn^- cell lines possessed higher vulnerability to the oxygen stress and exhibited higher production of hydroxyl radical than the parental p^+ cells. In the syn^- cells, extensive accumulation of deleted mtDNAs was demonstrated, compared with a smaller number of deleted mtDNAs in the parental p^+ cell. These in vitro culture studies demonstrate that the oxidative damage to mtDNA by the defective respiratory chain can be an underlying molecular mechanism in determining the cell death in human diseases caused by mtDNA mutations, or in aging.
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