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Studies on the tissue damage induced by activation of calpains under infarct/ischemia

Research Project

Project/Area Number 07670177
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya City University

Principal Investigator

SASAKI Makoto  Nagoya City University Medical School, Professor, 医学部, 教授 (10080003)

Co-Investigator(Kenkyū-buntansha) TADA Toyohiro  Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (20106230)
HAYAKAWA Tomihiro  Nagoya City University Medical School, Research Associate, 医学部, 助手 (50172995)
KUNIMATSU Mitoshi  Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (70145746)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsCalpain / Ischemia / Reperfusion / Calpain inhibitor / Miocardial infarction / NF-kappaB / Anti-calpain antibody / Neuronal cell death / 虚血再灌流 / μ-カルパイン前駆体 / 脳神経細胞死 / 神経芽細胞腫 / 心筋虚血再灌流 / NFχB
Research Abstract

The role of calpains in tissue damage and cell death under the conditions of infarction/ischemia was investigated. The initial study was carried out with rat heart, but later brains were employed as a target organ, because typical change was evidenced before and after ischemia.
1.Through ischemia/reperfusion of rat hearts, potential caseinolytic activity of calpains decreased to less than half in total, but the decrease was protected by the addition of calpain inhibitor I in the media before perfusion under ischemic conditions was carried out.
2.Various organ tissues were immunostained using antibodies against several antigenic determinants of mu- and m-calpains. The results showed that nuclei of neurons in both periferal and central nervous systems were densely stained and the staining mostly disappeared after ischemia/reperfusion. This change concided well with the degenerated areas elucidated by argyrophil III silver staining.
3.Densely stained nuclei were also observed with the cultured cells of neuroblasma cell lines and primary cultured neurons from rat brains. Neuronal cell death evaluated by the trypan blue exclusion test paralleled the disappearance of the staining. The cell death was time-dependent and it was efficiently prevented by the addition of calpain inhibitor I.
These results suggested that calpains may play a crucial role in the tissue damage induced by myocardial infarction and that exceptionally high sensitivity of brains to ischemic conditions may have a close relationship with the concentrated existence of pro mu-calpain in the nuclei of neurons.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] M.Kunimatsu et al.: "Neutrophil chemotactic N-acetyl peptides fron the calpain small subunit are also chemotactic for immunocytes" Biochem.Mol.Biol.Int.35. 247-254 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Onizuka et al.: "Distribution of μ-calpain proenzyme in the brain and other neural tissues in the rat" Brain Res.697. 179-186 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X-J.Ma et al.: "Putative mechanism for guinea pig ileum contaction by N-formyl peptides.A Comparative study of N-formyl-----" Life Sci.57. 463-471 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Z-Q.Liu et al.: "Proteolytic processing of nuclear factor κB by calpain in vitro" FEBS Lett.385. 109-113 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Onizuka et al.: "Early cytopathic features in rat ischemia model and reconstruction by neural graft" Exp.Neurol.137. 324-332 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 佐々木 實: "生体の科学" 金原一郎記念医学医療振興財団 代表者 伊藤正男, 494-496 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sasaki et al.: "Medical Aspects of Proteases and Protease Inhibitors" N.Katsunuma,H.Kido,H.Fritz and J.Travis, (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Kunimatsu, X-J.Ma, Y.Ozaki, M.Narita, M.Mizokami, M.Sasaki: "Neutrophil chemotactic N-acetyl peptides from the calpain small subunit are also chemotactic for immunocytes" Biochem.Mol.Biol.Int. 35. 247-254 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Onizuka, M.Kunimatsu, Y.Ozaki, K.Muramatsu, M.Sasaki, H.Nishino: "Distribution of m-calpain proenzyme in the brain and other neural tissues in the rat" Brain Res.697. 179-186 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X-J.Ma, M.Kunimatsu, Y.Ozaki, S.Fujimoto, M.Sasaki: "Putative mechanism for guinea pig ileum contraction by N-formyl peptides. A comparative study of N-formyl and N-acetyl peptides with the N-terminal sequence of the calpain small subunit" Life Sci.57. 463-471 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Z-Q.Liu, M.Kunimatsu, J-P.Yang, Y.Ozaki, M.Sasaki, T.Okamaoto: "Proteolytic processing of nuclear factor kappaB by calpain in vitro" FEBS Lett.385. 109-113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Onizuka, A.Fukuda, M.Kunimatsu, M.Kumazaki, M.Sasaki, A.Takaku, H.Nishino: "Early cytopathic features in rat ischemia model and reconstruction by neural graft" Exp.Neurol.137. 324-332 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sasaki et al..: Selective neuronal cell death induced by activation of mu-calpain under conditons of ischemia/reperfusion. IOS Press, 1997, eds.N.Katunuma et al. (in press),

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M. Kunimatsu et al.: "Neutrophil chemotactic N-acetyl peptides from the calpain small subunit are also chemotactic for immunocytes" Biochem. Mol. Biol. Int.35. 247-254 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] K. Onizuka et al.: "Distribution of μ-calpain proenzyme in the brain and other neural tissues in the rat" Brain Res.697. 179-186 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Z-Q. Liu et al.: "Proteolytic processing of nuclear factor κB by calpain in vitro" FEBS Lett.385. 109-113 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K. Onizuka et al.: "Early cytopathic features in rat ischemia model and reconstruction by neural graft" Exp. Neurol.137. 324-332 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M. Sasaki et al.: "Medical Aspects of Proteases and Protease Inhibitors" N. Katunuma, H. Kido, H. Fritz and J. Travis, (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Zhen-Qiu Liu et al.: "Proteolytic processing of nuclear factor kB by calpain in vitro" FEBS Letters. (in press).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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