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Role of DNA repair proteins in development of the tolerance after ischemic preconditioning

Research Project

Project/Area Number 15591507
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionAkita University

Principal Investigator

SUZUKI Akira  Akita University, School of Medicine, Assistant Professor, 医学部, 助手 (10311573)

Co-Investigator(Kenkyū-buntansha) KINOUCHI Hiroyuki  Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (30241623)
SUGAWARA Taku  Akita University, School of Medicine, Lecturer, 医学部, 講師 (80241660)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordscerebral ischemia / ischemic tolerance / hippocampal CA1 subregion / apoptosis / cytochrome c / caspases / APE / チトクロームC / cytochrome c / caspases
Research Abstract

Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the involvement of this protein in the development of neuronal tolerance to global cerebral ischemia after ischemic preconditioning. Adult male Sprague-Dawley rats were subjected to either 5 minutes of lethal global ischemia with or without 3 minutes of sublethal ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was histologically assessed, and DNA damage was visualized by in situ labeling of DNA fragmentation and DNA gel electrophoresis. APE expression was also examined by immunohistochemistry and Western blot analysis. Hippocampal CA1 neurons underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However, these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days after ischemic preconditioning. Immunohistochemistry showed virtually no constitutive expression of APE proteins in CA1 neurons ; however, ischemic preconditioning induced neuronal APE expression 1 to 3 days later. Western blot confirmed an increase in Ku 70 in this region at the same time. The temporal and spatial expression of APE corresponded to tolerance of the hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of APE protein in the development of neuronal tolerance after ischemic preconditioning.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 2003 Other

All Journal Article (9 results) Book (1 results) Publications (2 results)

  • [Journal Article] Candesartan reduces superoxide production after global cerebral ischemia2005

    • Author(s)
      Sugawara et al.
    • Journal Title

      Neuroreport 16

      Pages: 325-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Candesartan reduces superoxide production after global cerebral ischemia.2005

    • Author(s)
      Sugawara T, Kinouchi H, Oda M, Shoji H, Omae T, Mizoi K
    • Journal Title

      Neuroreport 16

      Pages: 325-328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neuronal death/survival signaling pathways in cerebral ischemia2004

    • Author(s)
      Sugawara T et al.
    • Journal Title

      NeuroRx 1

      Pages: 17-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mitochondrial cytochrome c-and Smac-dependent apoptosis in cerebral ischemia : role of oxidative signaling.2004

    • Author(s)
      Sugawara T, Ferrand-Drake M, Yu F, Maier C, Hoyte EE, Chan PH
    • Journal Title

      Maturation phenomenon in cerebral ischemia V.((eds) Buchan AM, Ito U, Colbourne F, Kuroiwa T, Klatzo I)(Springer-Verlag, Berlin)

      Pages: 53-62

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neuronal death/survival signaling pathways in cerebral ischemia.2004

    • Author(s)
      Sugawara T, Fujimura M, Noshita N, Kim GW, Saito A, Hayashi T, Narasimhan P, Maier C, Chan PH
    • Journal Title

      NeuroRx 1

      Pages: 17-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] カンデサルタンによる全脳虚血後の神経細胞死抑制効果2003

    • Author(s)
      菅原卓
    • Journal Title

      Therapeutic Research 24

      Pages: 1074-1077

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脳虚血とノックアウトモデル2003

    • Author(s)
      菅原卓, 木内博之, 溝井和夫
    • Journal Title

      分子脳血管病 2

      Pages: 99-105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The protective effects of candesartan on ischemic neuronal death after global cerebral ischemia2003

    • Author(s)
      Sugawara T
    • Journal Title

      Therapeutic Research 24

      Pages: 1074-1077

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cerebral ischemia and knockout animals2003

    • Author(s)
      Sugawara T, Kinouchi H, Oda M, Shoji H, Omae T, Mizoi K
    • Journal Title

      Molecular cerebrovascular disease 2

      Pages: 99-105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Maturation phenomenon in cerebral ischemia V2004

    • Author(s)
      Sugawara et al.
    • Total Pages
      362
    • Publisher
      Springer-Verlag, Berlin
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 菅原卓, 木内博之, 溝井和夫: "脳虚血とノックアウトモデル"分子脳血管病. 2・1. 99-105 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 菅原卓: "カンデサルタンによる全脳虚血後の神経細胞死抑制効果"Therapeutic Research. 24・6. 1074-1077 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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