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Alteration in HIF-1 DNA binding activity following cerebral ischemia and its therapeutic application

Research Project

Project/Area Number 14570617
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NOGAWA Shigeru  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50208310)

Co-Investigator(Kenkyū-buntansha) YASUTOMI Daisuke  Keio Universtiry, School of Medicine, Instructor, 医学部, 助手 (50348629)
DEMBO Tomohisa  Keio University, School of Medicine, Instructor, 医学部, 助手 (50306700)
TANAKA Kortaro  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (90129528)
鈴木 重明  慶應義塾大学, 医学部, 助手 (50276242)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsHIF-1 / iNOS / cerebral ischemia / rat / EMSA / 転写因子
Research Abstract

Because iNOS is expressed in the ischemic brain, we tried to determine whether binding activity of hypoxia inducible factor (HIF) -1 to hypoxia-responsive enhancer (HRE) is increased in ischemic brain in the rat employing the electrophoretic mobility shift assay (EMSA) technique.
One hour after 2-hour transient occlusion of the middle cerebral artery, hypoxia inducible factor (HIF) -1 binding activity was increased in the ischemic core and its surrounding area (penumbra). Six hours after ischemia, it was detected even in the contralateral hemisphere. In the penumbra, the activity was remained until 24 hours later, while it disappeared in the core. iNOS was induced during 12-48 hours after ischemia in the vessel walls and polymorphonuclear leukocytes within the ischemic territory.
Energy failure in the ischemic core and involvement of the other transcription factors such as IRF-1 and NFκB might explain the discrepancy between HIF-1 binding activity and iNOS induction after cerebral ischemia.

Report

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

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 野川 茂: "脳虚血と遺伝子発現"神経内科. 52. 18-27 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka K, Nogawa S, Ito D, et al.: "Phosphorylation of cyclic adenosine monophosphate response element binding protein in oligodendrocytes in the corpus callosum after focal cerebral ischemia in the rat."J Cereb Blood Flow Metab. 21. 1177-1188 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 田中耕太郎, 福内靖男, 野川茂, 他: "ブレイン・アタックの新しい治療戦略.病態より見た脳梗塞急性期治療のターゲット"臨床神経学. 41. 1052-1054 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nogawa S, Takao M, Suzuki S, et al.: "COX-2 expression in brains of patients with familial Alzheimer's disease."Excerpta Medica International Congress Series. Amsterdam : Elsevier Science. 1252. 363-372 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nogawa, S.: "Cerebral ischemia and gene expression"Shinkeinaika (Japanese). 52. 18-27 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka, K., Nogawa, S., Ito, D., et al.: "Phosphorylation of cyclic adenosine monophosphate response element binding protein in oligodendrocyte in the corpus callosum after focal cerebral ischemia in the rat."J Cereb Blood Flow Metab. 21. 1177-1188 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka, K., Fukuuchi, Y., Nogawa, S., et al.: "A new therapeutic strategy in brain attack ---Target of acute ischemic stroke treatment from the viewpoint of pathogenesis."Rinshoshinkeigaku (Japanese). 41. 1052-1054 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nogawa, S., Takao, M., Suzuki, S., et al.: "COX-2 expression in brains of patients with familial Alzheimer's disease."Excerpta Medica International Congress Series (Amsterdam : Elsevier Science). 1252. 363-372 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 野川 茂: "COX-2は中枢神経系でどのような働きをしているのですか?これだけは知っておきたいアラキドン酸カスケードQ&A.室田誠逸 編"医薬ジャーナル社,大阪. 4 (2002)

    • Related Report
      2002 Annual Research Report

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

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