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プロテオグリカンとコンドロイチン硫酸結合性タンパク質に関する統合的神経糖鎖生物学

Publicly Offered Research

Project AreaDeciphering sugar chain-based signals regulating integrative neuronal functions
Project/Area Number 24110501
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

菅原 一幸  北海道大学, 先端生命科学研究科(研究院), 学術研究員 (60154449)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords神経 / アルツハイマー病 / プロテオミクス / プロテオグリカン / コンドロイチン硫酸 / RAGE / グリコサミノグリカン / セマフォリン / デルマタン硫酸 / ヘパラン硫酸
Research Abstract

以前、コンドロイチン硫酸(CS)鎖中のEユニット構造が神経突起の伸長促進活性を有することを見出した。さらに、アルツハイマー病に関わるReceptor for Advanced Glycation End-products (RAGE)がCS-Eの受容体であることを同定した
本研究では、Receptor for Advanced Glycation End-products (RAGE)RAGEおよびコンドロイチン硫酸(CS)が関わる神経突起の伸長メカニズムを解明し、アルツハイマー病や神経再生の新しい研究分野の開拓を目指している。昨年度は、神経突起伸長活性を示すCS-Dから新規オリゴ糖を7種類単離し、脳のCSを認識する抗CS抗体と反応することを見出した。さらに、プロテオミクス解析によってCS鎖と結合する脳由来の新規タンパク質を複数同定した。また、非酵素的に酸・アルカリを使用せずにCSをオリゴ糖に低分子化する新技術を開発し、CS鎖中の機能ドメインの単離を加速させた。さらに、CS鎖をガラスの基盤に固相化し、CS鎖を含めたグリコサミノグリカン鎖のマイクロアレイを開発した。今年度は、セマフォリン3AがCS-Eと結合することで、ペリニューロナルネットの構築に寄与していることを見出した。さらに共同研究として、てんかん性の脳症がUDP-糖の輸送体をコードする遺伝子に変異が起きることで発症することを見出した。
以上の研究成果を国際誌に原著論文を5報発表した。また、国内学会発表2回、国際学会での発表を5回行った。

Current Status of Research Progress
Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (11 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines2013

    • Author(s)
      Shuji Mizumoto, Duriya Fongmoon, Kazuyuki Sugahara
    • Journal Title

      Glycoconjugate Journal

      Volume: in press Issue: 6 Pages: 619-632

    • DOI

      10.1007/s10719-012-9463-5

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A sulfated glycosaminoglycan array for molecular interactions between glycosaminoglycans and growth factors or anti-glycosaminoglycan antibodies2013

    • Author(s)
      Wataru Takada, Masao Fukushima, Peraphan Pothacharoen, Prachya Kongtawelert, Kazuyuki Sugahara
    • Journal Title

      Analytical Biochemistry

      Volume: 435 Issue: 2 Pages: 123-130

    • DOI

      10.1016/j.ab.2013.01.004

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mass preparation of oligosaccharides by hydrolysis of chondroitin sulfate polysaccharides with subcritical water microreaction system2013

    • Author(s)
      Shuhei Yamada, Keiichiro Matsushima, Haruo Ura, Nobuyuki Miyamoto, Kazuyuki Sugahara
    • Journal Title

      Carbohydrate Research

      Volume: 371 Pages: 16-21

    • DOI

      10.1016/j.carres.2013.01.024

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin 3A binds to the perineuronal nets via chondroitin sulfate type E motifs in rodent brains2013

    • Author(s)
      Gunnar Dick, Chin Lik Tan, Joao Nuno Alves, Erich M. E. Ehlert, Gregory M. Miller, Linda C. Hsieh-Wilson, Kazuyuki Sugahara, Arie Oosterhof, Toin H. van Kuppevelt, Joost Verhaagen, James W. Fawcett, and Jessica C. F. Kwok
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 38 Pages: 27384-27395

    • DOI

      10.1074/jbc.m111.310029

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy2013

    • Author(s)
      Kodera H, Nakamura K, Osaka H, Maegaki Y, Haginoya K, Mizumoto S, Kato M, Okamoto N, Iai M, Kondo Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, Sugahara K, Yuasa I, Wada Y, Matsumoto N, Saitsu H.
    • Journal Title

      Hum Mutat

      Volume: 34 Issue: 12 Pages: 1708-1714

    • DOI

      10.1002/humu.22446

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences with bioactivities2013

    • Author(s)
      Shuji Mizumoto, Saori Murakoshi, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, Shigeyuki Fukui, Prachya Kongtawelert, Shuhei Yamada, and Kazuyuki Sugahara
    • Journal Title

      Glycobiology

      Volume: 23 Issue: 2 Pages: 155-168

    • DOI

      10.1093/glycob/cws137

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitin sulfate wobble motifs modulate the maintenance and differentiation of neural stem cells and their progeny2012

    • Author(s)
      Purushothaman, A., Sugahara, K., and Faissner, A.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Issue: 5 Pages: 2935-2942

    • DOI

      10.1074/jbc.r111.298430

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mass preparation of chondroitin sulfate oligosaccharides by hydrolysis with subcritical water2013

    • Author(s)
      山田修平、松嶋景一郎、浦晴雄、宮本宣之、菅原一幸
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪国際交流センター(大阪)
    • Related Report
      2013 Annual Research Report
  • [Presentation] サメヒレ軟骨コンドロイチン硫酸由来の新規な六糖配列の単離2012

    • Author(s)
      ◯水本秀二, 村越早織, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, 福井成行, Prachya Kongtawelert, 山田修平, 菅原一幸
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2012-12-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] 硫酸化GAGマイクロアレイの開発およびGAGと成長因子/抗体との相互作用解析2012

    • Author(s)
      ○高田渉,福島雅夫, Peraphan Pothacharoen, Prachya Kongtawelert, 菅原一幸
    • Organizer
      第31回日本糖質学会年会
    • Place of Presentation
      鹿児島市民ホール(鹿児島市)
    • Year and Date
      2012-09-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences involved in brain development2012

    • Author(s)
      ○Shuji Mizumoto, Saori Murakoshi, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, Shigeyuki Fukui, Prachya Kongtawelert, Shuhei Yamada, and Kazuyuki Sugahara
    • Organizer
      2012年度 包括型脳科学研究推進支援ネットワーク・夏のワークショップ
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2012-07-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of a sulfated glycosaminoglycan array and analysis of molecular interactions between glycosaminoglycans and growth fractors/antibodies2012

    • Author(s)
      Wataru Takada, Masao Fukushima, Prachya Kongtawelert, and ○Kazuyuki Sugahara
    • Organizer
      The 15th Gordon Research Conference on Proteoglycans
    • Place of Presentation
      Proctor Academy(米国)
    • Year and Date
      2012-06-09
    • Related Report
      2012 Annual Research Report
  • [Presentation] Mass preparation of oligosaccharides with intestinal absorption capacity by hydrolysis of chondroitin sulfate polysaccharides with subcritical water microreaction system

    • Author(s)
      Kazuyuki Sugahara, Shuhei Yamada, Shuji Mizumoto, Keiichiro Matsushima, Haruo Ura, and Nobuyuki Miyamoto
    • Organizer
      The 13th International Conference on Functional and Medical Foods with Bioactive Compounds: Science and Practical Applications”
    • Place of Presentation
      The Kyoto Prefectural University of Medicine (Kyoto)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 亜臨界水を利用したコンドロイチン硫酸オリゴ糖の大量調製

    • Author(s)
      山田修平、松嶋景一郎、浦晴雄、宮本宣之、菅原一幸
    • Organizer
      59回日本薬学会東海支部 総会・大会
    • Place of Presentation
      名城大学薬学部(名古屋)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage. Insights into the sugar sequences involved in brain development

    • Author(s)
      Kazuyuki Sugahara
    • Organizer
      The 8th International Conference on Proteoglycans
    • Place of Presentation
      Hotel Collegium Glashutten(ドイツ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Wobble chondroitin sulfate oligosaccharide motifs and mass production of oligosaccharides

    • Author(s)
      Kazuyuki Sugahara
    • Organizer
      The 21st Symposium on Glycosaminoglycans
    • Place of Presentation
      Loveno, Lake Como(イタリア)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Novel chondroitin sulfate oligosaccharide motifs as biomarkers: Insights into their involvement in the brain development

    • Author(s)
      Kazuyuki Sugahara and Shuji Mizumoto
    • Organizer
      The 10th International Symposium on Cell Surface Macromolecules
    • Place of Presentation
      Fortune Park Panchwat(インド)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Integrated neuroglycobiology for proteoglycans and chondroitin sulfate-binding proteins

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, Yusuke Yoshikawa, Shuhei Yamada, Kosei Takeuchi, Yoshiaki Nakayama, Akira Kurosaka, Keiichiro Matsushima, Nobuyuki Miyamoto, Wataru Takada, Hirofumi Kodera, Naomichi Matsumoto, Hirotomo Saitsu, Gunnar Dick, James W. Fawcett, and Jessica C. F. Kwok
    • Organizer
      nternational Symposium on Glyco-Neuroscience
    • Place of Presentation
      Awaji Yumebutai International Conference Center(淡路)
    • Related Report
      2013 Annual Research Report
  • [Remarks] 研究業績

    • URL

      http://www.lfsci.hokudai.ac.jp/labs/infmem/sugaken/lonbun.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2013-05-15   Modified: 2019-07-29  

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