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周生期脳障害の抑制効果を示す機能性糖鎖の同定と作用機序の解析

Research Project

Project/Area Number 14657260
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Embryonic/Neonatal medicine
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center

Principal Investigator

大平 敦彦  愛知県心身障害者コロニー発達障害研究所, 周生期学部, 部長 (20101074)

Co-Investigator(Kenkyū-buntansha) 松井 ふみ子  愛知県心身障害者コロニー・発達障害研, 究所・周生期学部, 助手
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords脳障害 / プロテオグリカン / コンドロイチン硫酸 / 神経系前駆細胞 / FGF-2 / 細胞増殖 / 脳損傷 / 虚血 / 低酸素 / 細胞内骨格タンパク / 神経前駆細胞 / ホスファカン / 新生児 / NGC
Research Abstract

本研究の目的は、プロテオグリカン、特にそのコンドロイチン硫酸(CS)糖鎖を利用して、周生期脳障害の新たな早期治療法への道を拓くことである。この目的に向かって、本年度は、以下の成果を上げた。
1.コンドロイチン硫酸による神経系前駆細胞の機能調節
神経系前駆細胞のニューロスフェアー培養系に、FGF-2と共に種々の市販CS標品を添加したところ、CS-BおよびCS-Eがヘパリンやヘパラン硫酸と同程度の増殖促進効果を持つことを発見した。さらに、驚くべきことに、神経系前駆細胞に富む胎生14日ラット胎仔脳由来のCS標品にも、FGF-2依存性の神経系前駆細胞の増殖を促進する活性が認められた。このCS標品は、CS-B由来の二糖単位(B-unit)を約5%、CS-E由来の高硫酸化二糖単位(E-unit)を2%弱含む。このことから、これら二糖単位が構成する機能領域が、胎仔脳由来のCSには存在することが示唆された。
2.コンドロイチン硫酸機能領域の検索
CS-BおよびCS-E多糖鎖中の、神経系前駆細胞増殖促進活性領域を同定することを目指して、CS-Bを亜硝酸/ヒドラジン分解により、また、CS-Eを精巣性ビアルロニダーゼ消化により、分子サイズの異なるオリゴ糖を調製した(弘前大学・高垣啓一教授による)。いずれのオリゴ糖も、FGF-2の活性を増強しなかった。一方、CS-BとFGF-2存在下で、CS-B由来オリゴ糖を添加した場合、二糖画分がCS-B多糖によるFGF-2の活性増強を抑制した。また、CS-EおよびFGF-2存在下で、CS-E由来オリゴ糖を添加した時には、六糖および四糖画分がCS-E多糖によるFGF2の活性増強を抑制した。この結果から、FGF-2依存性の細胞増殖を促進するためには、CS-BとCS-Eは多糖であることが心要である。しかし、その活性発現に必須な機能領域は、二〜六糖程度の低分子と思われる。

Report

(3 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 Other

All Journal Article (6 results) Book (1 results) Patent(Industrial Property Rights) (1 results) Publications (12 results)

  • [Journal Article] Neuronal expression of the chondroitin sulfate proteoglycans receptor-type protein-tyrosine phosphatase β and phosphacan.2005

    • Author(s)
      Noriko Hayashi
    • Journal Title

      Neuroscience 131

      Pages: 331-348

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Heparan sulfate proteoglycans interact with neurocan and promote neurite outgrowth from cerebellar granule cells.2004

    • Author(s)
      Kaoru Akita
    • Journal Title

      Biochemical Journal 383(Pt.1)

      Pages: 129-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Developmental changes in the biochemical and immunological characters of the carbohydrate moiety of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan.2004

    • Author(s)
      Takuya Shuo
    • Journal Title

      Glycoconjugate Journal 20

      Pages: 267-278

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activity-dependent regulation of a chondroitin sulfate proteoglycan 6B4 phosphacan/RPTPβ in the hypothalamic supraoptic nucleus.2004

    • Author(s)
      Seiji Miyata
    • Journal Title

      Brain Research 1017

      Pages: 163-171

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroglycan C, a novel member of the neuregulin family.2004

    • Author(s)
      Yumi Kinugasa
    • Journal Title

      Biochemical and Biophysical Research Communications 321

      Pages: 1045-1049

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Glycosylation site for chondroitin sulfate on the neural part-time proteoglycan, neuroglycan C.2004

    • Author(s)
      Sachiko Aono
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 46536-46541

    • Related Report
      2004 Annual Research Report
  • [Book] 「蛋白質核酸酵素」増刊号「神経糖鎖生物学」分担編集および分担執筆2004

    • Author(s)
      大平 敦彦
    • Total Pages
      222
    • Publisher
      共立出版株式会社
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2004

    • Inventor(s)
      大平 敦彦他
    • Industrial Property Rights Holder
      生化学工業(株)
    • Industrial Property Number
      2004-228692
    • Filing Date
      2004-08-04
    • Related Report
      2004 Annual Research Report
  • [Publications] Kazunori Sango 他: "Phosphacan and neurocan are repulsive substrata for adhesion and neurite extension of adult rat dorsal root ganglion---"Experimental Neurology. 182(1). 1-11 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahisa Koga 他: "Expression of glycosaminoglycans during development of the rat retina."Current Eye Research. 27(2). 75-83 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Motoi Okamoto 他: "Kainic acid-induced convulsions cause prolonged changes in the chondroitin sulfate proteoglycans neurocan and---"Experimental Neurology. 184(1). 179-195 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Keiko Nakanishi 他: "Altered synaptic activities in cultures of neocortical neurons from prenatally X-irradiated rats."Neuroscience Letters. 355(1-2). 61-64 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takuya Shuo 他: "Developmental changes in the biochemical and immunological characters of the carbohydrate moiety of neuroglycan C---"Glycoconjugate Journal. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seiji Miyata 他: "Activity-dependent downregulation of a chondroitin sulfate proteoglycan 6B4 phosphacan/RPTPβ in the hypothalamic---"Neuroscience. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaru Inatani et al.: "Spatiotemporal expression patterns of N-syndecan, a transmembrane heparan sulfate preteoglycan, in developing retina"Investigative Ophthalmology & Visual Science. 41(5). 1616-1621 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seiji Miyata et al.: "Chondroitin sulfate proteoglycan phosphacan/RPTP in the hypothalamic magnocellular nuclei"Brain Research. 949(1-2). 112-121 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fumiko Matsui et al.: "Transient expression of juvenile-type neurocan by reactive astrocytes in adult rat brains injured by kainate-induced seizures as well as ---"Neuroscience. 112(4). 773-781 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoko Toba et al.: "Expression and immunohistochemical localization of heparan sulphate proteoglycan N-syndecan in the migratory pathway from ---"European Journal of Neuroscience. 15(9). 1461-1473 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sinobu Tamauchi et al.: "Phosphorylation of neuroglycan C, a brain-specific transmembrane chondroitin sulfate proteoglycan, and its localization in the lipid rafts"Journal of Biological Chemistry. 277(23). 20583-20590 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazunori Sango et al.: "Phosphacan and neurocan are repulsive substrates for adhesion and neurite extension of adult rat dorsal root ganglion neurons in vitro"Experimental Neurology. (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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