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Impairment of axonal transport of mitochondria and axonal degeneration induced by free radicals

Research Project

Project/Area Number 16500267
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionKitasato University

Principal Investigator

KAWAKAMI Tadashi  Kitasato University, School of Medicine, Professor, 医学部, 教授 (60177649)

Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
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)
Keywordsaxonal transport / axonal degeneration / mitochondria / free radicals / superoxide dismutase / 軸策輸送
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.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (8 results)

All 2007 2006 2005 2004 Other

All Journal Article (8 results)

  • [Journal Article] Vesicle disruption, plasma membrane bleb formation, and acute cell death caused by illumination with blue light in acridine orange-loaded malignant melanoma cells2007

    • Author(s)
      Hiruma H, Katakura T, Takenami T, Igawa S, Kanoh M, Fujimura T, Kawakami T
    • Journal Title

      Journal of Photochemistry and Photobiology B, Biology 86(1)

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Vesicle disruption, plasma membrane bleb formation, and acute cell death caused by illumination with blue light in acridine orange-loaded malignant melanoma cells2007

    • Author(s)
      Hiruma H, Katakura T, Takenami T, Igawa S, Kanoh M, Fujimura T, Kawakami T
    • Journal Title

      Journal of Photochemistry and Photobiology B Biology 86(1)

      Pages: 1-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitric oxide synthase activity in rat gastric mucosa contributes to mucin synthesis elicited by calcitonin gene-related peptide2006

    • Author(s)
      Ichikawa T, Kusakabe T, Gono Y, Shikama N, Hiruma H, Kawakami T, Ishihara K
    • Journal Title

      Biomedical Research (Tokyo, Japan) 27(3)

      Pages: 117-124

    • NAID

      130004470657

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Effects of soluble laminin on organelle transport and neurite growth in cultured mouse dorsal root ganglion neurons : difference between primary neurites and branches2005

    • Author(s)
      Kohno K, Kawakami T, Hiruma H
    • Journal Title

      Journal of Cellular Physiology 205(2)

      Pages: 253-261

    • NAID

      130005448019

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Neurotoxicity of intrathecally administered bupivacaine involves the posterior roots/posterior white matter and is milder than lidocaine in rats2005

    • Author(s)
      Takenami T, Yagishita S, Murase S, Hiruma H, Kawakami T, Hoka S
    • Journal Title

      Regional Anesthesia and Pain Medicine 30(5)

      Pages: 464-472

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neurotoxicity of intrathecally administered bupivacaine involves the posterior roots/posterior white matter and is milder than lidocaine in rats.2005

    • Author(s)
      Takenami T, Yagishita S, Murase S, Hiruma H, Kawakami T, Hoka S
    • Journal Title

      Regional Anesthesia and Pain Medicine 30(5)

      Pages: 464-472

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cells.2004

    • Author(s)
      Igawa S, Hayashi I, Tanaka N, Hiruma H, Majima M, Kawakami T, Hirose M, Masuda N, Kobayashi H.
    • Journal Title

      Cancer Science 95(4)

      Pages: 342-347

    • NAID

      10013722547

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of Soluble Laminin on Organelle Transport and Neurite Growth in Cultured Mouse Dorsal Root Ganglion Neurons : Difference between Primary Neurites and Branches

    • Author(s)
      Kohno K, Kawakami T, Hiruma H
    • Journal Title

      Journal of Cellular Physiology (発表予定)

    • NAID

      130005448019

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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