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A new approach for treatments against central nervous disease : Structure of albumin-derived microglial activating factor

Research Project

Project/Area Number 10558114
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Neurochemistry/Neuropharmacology
Research InstitutionEHIME UNIVERSITY

Principal Investigator

NAKAMURA Yoichi  Ehime University. School of Medicine, Assistant Professor, 医学部, 助手 (90180413)

Co-Investigator(Kenkyū-buntansha) 片岡 喜由  愛媛大学, 医学部, 教授 (20025589)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsmicroglia / phorbol ester / brain ischemia / albumin / tetrapeptide / macrophage / serum factor / superoxide anion / 活性酸素 / 血清アルブミン / ケモカイン / 生理活性ペプチド
Research Abstract

Microglial activation has recently been recognized as a cause of damage in various neurodegenerative diseases. A possible mechanism underlying this damage is the activation of microglia by serum factors leaked through a disruption of the blood-brain barrier, which in turn trigger microglial cell proliferation and the release of various substances toxic to neurons, such as superoxide (OィイD22ィエD2). We recently reported that serum albumin enhanced OィイD22ィエD2 production in cultured rat microglia stimulated by phorbol ester (Si e al., 1997, Glia 21 : 413-418). In the present report, we identify the active site of this enhancement within the albumin molecule. We purified an active subfragment from trypsin-treated bovine serum albumin (BSA) that was composed of 12-mer and 33-mer peptides connected by a disulfide bond. The chemically synthesized 12-mer peptide showed activity within a concentration range (ca. 10ィイD1-7ィエD1 M) equivalent to that of albumin. The activities of a series of synthesized peptides conclusively indicated that the minimum active sequence was Leu-His-Thr-Leu. Enhancement of OィイD22ィエD2 production by this peptide was also observed in macrophages quiescently prepared from rat peritoneal fluid. The present study may contribute toward the development of a tool to suppress the pathological activation of microglia and may also shed light on albumin's role in the biological defense system.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Si,Q.-S,.Nakamura,Y.,Ogata,T.Schubert,P.,Kataoka,K.: "Differential Regulation of Microglial Activation by Propentofylline via cAMP Signaling."Brain Research. 812. 97-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura,Y.,Si,Q.-S.,Kataoka,K.: "Lipopolysaccharide-induced Microglial Activation in Culture:Temporal Profiles of Morphological Change and Release of Cytokines and Nitric Oxide."Neuroscience Research,. 35. 95-100 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Si,Q.-S.,Nakamura,Y.,Kataoka,K.: "A Serum Factor Enhances Production of Nitric Oxide and Tumor Necrosis Factor-α from Cultured Microglia"Experimental Neurology. (印刷中). 97-104 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 中村洋一,司秋生,片岡喜由: "ミクログリア活性化と神経細胞障害"脳の科学. 20. 385-391 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 中村洋一,片岡喜由: "シナプス伝達におけるグリアの役割"Clinical Neuroscience. 16. 990-992 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 中村洋一,司秋生,片岡喜由: "グリア活性化因子"Clinical Neuroscience. 17. 1013-1016 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Si, Q.-S., Nakamura, Y., Ogata, T. Schubert, P., Kataoka. K.: "Differential Regulation of Microglial Activation by Propentofylline via cAMP Signaling"Brain Research. 812. 97-104 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, Y., Si, Q.-S., Kataoka, K.: "Lipopolysaccharide-induced Microglial Activation in Culture : Temporal Profiles of Morphological Change and Release of Cytokines and Nitric Oxide"Neuroscience Research. 35. 95-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Si, Q.-S., Nakamura, Y., Kataoka, K.: "A Serum Factor Enhances Production of Nitric Oxide and Tumor Necrosis Factor-α from Cultured Microglia"Experimental Neurology. (in press). 97-104 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, Y., Si, Q-S, Kataoka, K: "Microglial activation and neuronal damage (Japanese, Review)"Nou-no-Kagaku. 20. 385-391 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, Y., Si, Q-S, Kataoka, K: "Role of glial cells in synaptic transmission (Japanese, Review)"Clinical Neuroscience. 16. 990-992 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, Y., Si, Q-S, Kataoka, K: "Factors for glial activation (Japanese, Review)"Clinical Neuroscience. 17. 1013-1016 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Si,Q.-S.,Nakamura,Y.,Ogata,T.Schubert,P.,Kataoka,K.: "Differential Regulation of Microglial Activation by Propentofylline via cAMP Signaling."Brain Research. 812. 97-104 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,Y.,Si,Q.-S.,Kataoka,K.: "Lipopolysaccharide-induced Microglial Activation in Culture:Temporal Profiles of Morphological Change and Release of Cytokines"Neuroscience Research,. 35. 95-100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Si,Q.-S.,Nakamura,Y.,Kataoka,K.: "A Serum Factor Enhances Production of Nitric Oxide and Tumor Necrosis Factor-α from Cultured Microglia"Experimental Neurology. (印刷中). 97-104 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中村 洋一,司 秋生,片岡 喜由: "ミクログリア活性化と神経細胞障害"脳の科学. 20. 385-391 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中村 洋一,片岡 喜由: "シナプス伝達におけるグリアの役割"Clinical Neuroscience. 16. 990-992 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中村洋一,司秋生,片岡喜由: "グリア活性化因子"Clinical Neuroscience. 17. 1013-1016 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Qiu-Sheng Si,Yoichi Nakamura,Kiyoshi Kataoka: "Albumin Enhances Superoxide Production in Cultured Microglia" Glia. 21. 413-418 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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