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DNA double-strand breaks in inclusion body myositis

Research Project

Project/Area Number 18590960
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKansai Medical University

Principal Investigator

NAKANO Satoshi  Kansai Medical University, Neurology, Assistant Professor (30333206)

Co-Investigator(Kenkyū-buntansha) SHINDE Akiyo  Kansai Medical University, Neurology, Instructor (10368235)
ITO Hidefumi  Kansai Medical University, Neurology, Associate Professor (20250061)
KUSAKA Hirofumi  Kansai Medical University, Neurology, Professor (70250066)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,320,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsNeurology / Myopathy / Pathology / DNA double-strand breaks
Research Abstract

Objectives: To examine DNA damage response in s-IBM. Background: In sporadic inclusion body myositis, several studies have indicated that myonuclear abnormality may be closely associated with its pathogenesis. Materials & Methods: Immunhistochemistry in biopsy materials from patients with s-IBM (n=17), polymyositis (15), dermatomyositis (10) and other controls (10). Antibodies against 1) phosphorylated histone H2AX (γH2AX) that accumulates to the damaged sites with DNA double-strand breaks (DSB); and 2) DNA-PK that is an enzyme involved in DSB repair. DNA-PK consists of a catalytic subunit (DNA-PKcs) and regulatory subunits (Ku70 and Ku80). Results: In s-IBM and other myositis controls, a proportion of myonuclei showed strong immunoreactivity of γH2AX and DNA-PK while normal controls showed weak myonuclear reactivity. In muscle fibers with vacuoles in s-IBM, vacuolar rims were frequently positive for γH2AX and DNA-PK. Whereas DNA-PKcs and Ku80 were associated with DNA in vacuolated fibers, Ku70 was observed in the cytoplasm as inclusions. Conclusions: DSB occurs in some myonuclei in inflammatory myopathies. In s-IBM, the cytoplasmic accumulation of Ku70 regulatory component of DNA-PK may prevent their translocation to the nucleus and DSB sites. Accumulation of DSB may lead to the myonuclear degeneration in s-IBM.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (29 results)

All 2008 2007 2006 2005

All Journal Article (11 results) (of which Peer Reviewed: 8 results) Presentation (16 results) Book (2 results)

  • [Journal Article] Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis2008

    • Author(s)
      Nakano S., et. al.
    • Journal Title

      Neuromuscul Disord 18

      Pages: 27-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of caveolar components in primary desminopathy2008

    • Author(s)
      Shinde A., et. al.
    • Journal Title

      Neuromuscul Disord 18

      Pages: 215-219

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phosphorylated Smad2/3 immunoreactivity in sporadic and familial amyotrophic lateral sclerosis and its mouse model2008

    • Author(s)
      Nakamura M., et. al.
    • Journal Title

      Acta Neuropathol 115

      Pages: 327-334

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Histone HI is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis2008

    • Author(s)
      Nakano S., et. al.
    • Journal Title

      Neuromuscul Disord 18

      Pages: 27-33

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylated Smad2/3 immunoreactivity in sporadic and familial amy otrophic lateral sclerosis and its mouse model2008

    • Author(s)
      Nakamura M., et. al.
    • Journal Title

      Acta Neuropathol 115

      Pages: 327-334

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation2007

    • Author(s)
      Ito H., et. al.
    • Journal Title

      Acta Neurol Scand. 115

      Pages: 271-274

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation.2007

    • Author(s)
      Ito H., et al.
    • Journal Title

      Acta Neurol Scand 115(4)

      Pages: 271-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Altered distributions of nucleocytoplasmic transport-related proteins in the spinal cord of a mouse model of amyotrophic lateral sclerosis2006

    • Author(s)
      Zhang J., et. al.
    • Journal Title

      Acta Neuropathol 112

      Pages: 673-680

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 左被殻出血により両側性味覚障害をきたした1例2006

    • Author(s)
      伊藤 恒, 他
    • Journal Title

      臨床神経学 46

      Pages: 288-290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Altered distributions of nucleocytoplasmic transport-related proteins in the spinal cord of a mouse model of amyotrophic lateral sclerosis.2006

    • Author(s)
      Zhang J., et al.
    • Journal Title

      Acta Neuropathol(Berl) 112(6)

      Pages: 673-80

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Biolateral gustatory disturbance associated with left putaminal hemorrhage2006

    • Author(s)
      Ito H., et al.
    • Journal Title

      Rinsho Shinkeigaku 46(4)

      Pages: 288-90

    • Related Report
      2006 Annual Research Report
  • [Presentation] 炎症性ミオパチーにおけるDNA2本鎖切断の証明:γ-H2AXの免疫組織化学による検討2008

    • Author(s)
      西井 誠, 他
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] DNA double-strand breaks in inflammatory myopathies.2008

    • Author(s)
      Nishii M, et. al.
    • Organizer
      49th Ann. Meeting of Japanese Society of Neurology
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 封入体筋炎におけるヒストンの異常2007

    • Author(s)
      中野 智, 他
    • Organizer
      第39回日本臨床分子形態学会総会・学術集会
    • Place of Presentation
      山梨
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 炎症性ミオパチーにおけるDNA2本鎖切断の証明:γ-H2AXの免疫組織化学による検討2007

    • Author(s)
      中野 智, 他
    • Organizer
      第48回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 封入体筋炎とDMRVにおけるO-GlcNAc転移酵素の異常発現2007

    • Author(s)
      中野 智, 他
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Abnormality of histones in inclusion body myositis.2007

    • Author(s)
      Nakano S, et. al.
    • Organizer
      39th Ann. Meeting of Japanese Society of Medical Molecular Morphology
    • Place of Presentation
      Kofu
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] DNA double-strand breaks in inflammatory myopathies using γ-H2AX immunohistochemisty.2007

    • Author(s)
      Nakano S, et. al.
    • Organizer
      48th Ann. Meeting of Japanese Society of Neuropathology
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Myopathy with nemaline bodies, apoptotic changes, and immunohisto-chemical reactions similar to those in myofibrillar myopathy.2007

    • Author(s)
      Nakano S, et. al.
    • Organizer
      48th Ann. Meeting of Japanese Society of Neuropathology
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] O-G1cNAc transferase in inclusion body myositis and DMRV.2007

    • Author(s)
      Nakano S, et. al.
    • Organizer
      48th Ann. Meeting of Japanese Society of Neurology
    • Place of Presentation
      Nagoya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 炎症性ミオパチーにおけるDNA2本鎖切断の証明:γ-H2AXの免疫組織化学による検討2006

    • Author(s)
      中野 智, 他
    • Organizer
      第38回日本臨床分子形態学会総会・学術集会
    • Place of Presentation
      山口
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 封入体筋炎とDMRVにおける縁取り空胞は核由来である2006

    • Author(s)
      中野 智, 他
    • Organizer
      第47回日本神経学会総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Myofibrillar myopathyにおけるcaveolin-3とlipid raftsの分布2006

    • Author(s)
      新出 明代, 他
    • Organizer
      第47回日本神経学会総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Myopathy associated with apoptotic nuclei and nemaline bodies.2006

    • Author(s)
      Nakano S, et. al.
    • Organizer
      38th Ann. Meeting of Japanese Society of Medical Molecular Morphology
    • Place of Presentation
      Yamaguchi
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Rimmed vacuoles in inclusion body myositis and DMRV originate from the nucleus.2006

    • Author(s)
      Nakano S, et. al.
    • Organizer
      47th Ann. Meeting of Japanese Society of Neurology
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Caveolin-3 and lipid rafts in myofibrillar myopathy.2006

    • Author(s)
      Shinde A, et. al.
    • Organizer
      47th Ann. Meeting of Japanese Society of Neurology
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Nemaline小体と核のapoptotic changeを伴い、myofibrillar myopathy様の免疫組織化学反応を示したミオパチー2005

    • Author(s)
      中野 智, 他
    • Organizer
      第48回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] わかりやすい内科学 第3版2008

    • Author(s)
      井村 裕夫編
    • Total Pages
      1481
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] わかりやすい内科学第3版2008

    • Author(s)
      井村 裕夫, 編
    • Total Pages
      1481
    • Publisher
      文光堂
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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