| Project/Area Number |
10832008
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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 |
老化(加齢)
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| Research Institution | Tokai University |
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Principal Investigator |
ISHII Naoaki Tokai University Associate School of Medicine Professor, 医学部, 助教授 (60096196)
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| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Oxidative stress / Aging / C.elegans / Mitochondria / Cytochrome b / Electron transport / Complex II / life-span / 酸化タンパク質 / 突然変異 |
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| Research Abstract |
Much attention has been focused on the hypothesis that oxidative damage contributes to cellular and organismal aging. A mev-1 (kn1) mutant of the nematode Caenorhabditis elegans was isolated on the basis of its methyl viologen (paraquat) hypersensitivity and was also shown to be hypersensitive to hyperoxia. Unlike with wild type, its life span decreased dramatically as oxygen concentrations were increased from 1% to 60%. Strains bearing this mutation accumulated fluorescent materials and protein carbonyl groups, markers of aging, at faster rates than the wild type. We cloned mev-1 gene by transformation rescue and found that it is the previously sequenced gene (cyt-1) that encodes succinate dehydrogenase cytochrome b. The kn1 allele is a missense mutation that abolished complex II activity in the mitochondrial membrane but not succinate dehydrogenase enzyme activity per se. There are two important sets of biochemical changes in mev-1 animals that serve to explain these two phenotypes : 1) an overproduction of superoxide anion and a reciprocal reduction in glutathione content ; and 2) abnormalities in energy metabolism that likely lead to lactic acidosis. These data indicate that Cyt-1 plays an important role in the energy metabolism and protection from the oxidative stress.
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