Impairment of axonal transport of mitochondria and axonal degeneration induced by free radicals
| Project/Area Number |
16500267
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Kitasato University |
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Principal Investigator |
KAWAKAMI Tadashi Kitasato University, School of Medicine, Professor, 医学部, 教授 (60177649)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | axonal transport / axonal degeneration / mitochondria / free radicals / superoxide dismutase / 軸策輸送 |
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| Research Abstract |
Energy required for keeping function and morphology in neurons are provided by mitochondria. Neurons have axons, therefore, for providing energy, mitochondria should be carried by axonal transport. When transport of mitochondria in axon is impaired, various pathological conditions occur. Especially, axonal degeneration is closely related to impairment of mitochondrial transport. Mitochondria release amounts of free radicals during providing ATP through aerobic respiration. Nitric oxide, one of free radicals, has cellular toxicity and is removed by superoxide dismutase (SOD), a mitochondrial enzyme. The present study examined the influence of free radicals on axonal transport of mitochondria. Video-enhanced microscopy was used for experiments. The nitric oxide donor NOC18 inhibited anterograde and retrograde axonal transport of mitochondria. The SOD inhibitor diethyldithio carbamate also inhibited mitochondrial transport and induced axonal degeneration. The nitric oxide increased mitochondrial transport. Thus, intrinsic nitric oxide tonically inhibits mitochondrial transport. The hydroxyl radical scavenger dimethyl thiourea did not affect mitochondrial transport, suggesting that they are not related to impairment of mitochondrial transport. This may be because hydroxyl radicals can exist for only microseconds. The present study indicates that intrinsic and extrinsic free radicals inhibit mitochondrial transport. Since impairment of mitochondrial transport leads to axonal degeneration, abnormally increased free radicals may impair mitochondrial transport, causing degeneration in neurons.
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Report
(4 results)
Research Products
(8 results)
