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Endoplasmic reticulum stress-induced apoptosis in pre-necrotic period in skeletal muscles of laminin-2 deficiency

Research Project

Project/Area Number 14570605
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

IKEZOE Koji  KYUSHU UNIVERSITY, Hospital, Research Associate, 大学病院, 助手 (80343317)

Co-Investigator(Kenkyū-buntansha) FURUYA Hirokazu  KYUSHU UNIVERSITY, Graduated School of Medical Sciences, Associate Professor, 大学院・医学研究院, 助教授 (60253415)
TAKEDA Shinichi  National Center of Neurology and Psychiatry, Institute of Neurosciencies, Head, 神経研究所, 部長(研究職) (90171644)
川尻 真和  九州大学, 医学部附属病院, 助手 (00335960)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsapoptosis / laminin-2 / merosin / anoikis / Bad / caspase-12 / ER stress / 小胞体ストレス性アポトーシス / 筋小胞体 / ジスフェルリン / 筋ジストロフィー
Research Abstract

Abortive regeneration process following massive necrosis in perinatal period causes dystrophic changes in laminin-2 deficient skeletal muscles. Although this apoptotic muscle fiber loss seems to be anchorage-dependent or anoikis, defective signaling pathways resulting in apoptosis have not been identified, yet.
In this study, we examined the signaling pathways disturbed in regenerating fibers of dy3K/dy3K, a null mutant mouse for laminin a2 chain. Regenerating fibers of dy3K/dy3K showed phosphorylation of Ser 112 and 135 of Bad, but of Ser 155. Ser 155 of Bad is phosphorylated via activation of PKA. Therefore, it is possible that the survival signaling pathway via PKA is disturbed in regenerating fibers of dy3K/dy3K.
In addition, we examined skeletal muscles in the pre-necrosis period of dy3K/dy3K. In dy3K/dy3K, massive necrosis occurs suddenly on postnatal day 10. We found the activation of caspase-12 on postnatal day 9. Accordingly, the endoplasmic reticulum (ER) stress-induced apoptosis seems to take place just before the necrosis of muscle fibers in dy3K/dy3K.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (16 results)

All 2004 2003 2002 Other

All Journal Article (12 results) Publications (4 results)

  • [Journal Article] Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy2004

    • Author(s)
      Ikezoe k et al.
    • Journal Title

      Acta Neuropathol (Berl) 107

      Pages: 439-442

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] HTLV-1-associated myelopathy/tropical spastic paraparesis accompanied with psoriasis2004

    • Author(s)
      Watanabe A et al.
    • Journal Title

      J Neurol Sci 221

      Pages: 95-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A case of dermato-fasciitis : amyopathic dermatomyositis associated with fasciitis2004

    • Author(s)
      Tsuruta Y et al.
    • Journal Title

      Clin Rheumatol 23

      Pages: 160-162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 成人期に増悪した良性先天型ネマリンミオパチーで、生検筋に縁取り空胞と筋電図上神経原性所見のみを呈した1例2004

    • Author(s)
      池添浩二 他
    • Journal Title

      臨床神経 44

      Pages: 450-453

    • NAID

      10013426805

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy.2004

    • Author(s)
      Ikezoe K, et al.
    • Journal Title

      Acta Neuropathol (Berl) 107(5)

      Pages: 439-442

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A case of dermato-fasciitis : amyopathic dermatomyositis associated with fasciitis.2004

    • Author(s)
      Tsuruta Y, et al.
    • Journal Title

      Clin Rheumatol 23(2)

      Pages: 160-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] HTLV-1-associated myelopathy/tropical spastic pararesis accompanied with psoriasis.2004

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

      J Neurol Sci 221(1-2)

      Pages: 95-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dysferlin expression in tubular aggregates : their possible relationship to endoplasmic stress2003

    • Author(s)
      Ikezoe k et al.
    • Journal Title

      Acta Neuropathol (Berl) 105

      Pages: 603-609

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dysferlin expression in tubular aggregates: their possible relationship to endoplasmic reticulum stress.2003

    • Author(s)
      Ikezoe K, et al.
    • Journal Title

      Acta Neuropathol (Berl) 105(6)

      Pages: 603-609

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Apoptosis is suspended in muscle of mitochondrial encephalomyopathies2002

    • Author(s)
      Ikezoe K et al.
    • Journal Title

      Acta Neuropathol (Berl) 103

      Pages: 530-540

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Apoptosis is suspended in muscle of mitochondrial encephalomyopathies.2002

    • Author(s)
      Ikezoe K et al.
    • Journal Title

      Acta Neuropathol (Berl) 103(6)

      Pages: 531-540

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Increased membrane permeability in early postnatal period of laminin alpha2 chain-null mice, dy^<3K>/dy^<3K>.2002

    • Author(s)
      Nakagawa M et al.
    • Journal Title

      Acta Myologica XX(2)

      Pages: 167-173

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikezoe K et al.: "Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy"Acta Neuropathol(Ber1). (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe A et al.: "HTLV-1-associated myelopathy/tropical spastic paraparesis accompanied with psoriasis"J Neurol Sci. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuruta Y et al.: "A case of dermato-fasciitis : amyopathic dermatomyositis associated with fasciitis"Clin Rheumatol. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikezoe K, Furuya H, Ohyagi H, et al.: "Dysferlin expression in tubular aggregates : their possible relationship to ER stress"Acta Neuropathol (Berl). (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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