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Structural and functional studies on the novel hyaluronidase trying for its clinical application

Research Project

Project/Area Number 24590071
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionMeijo University

Principal Investigator

YAMADA Shuhei  名城大学, 薬学部, 教授 (70240017)

Co-Investigator(Renkei-kenkyūsha) SUGAHARA Kazuyuki  北海道大学, 先端生命科学研究院, 名誉教授 (60154449)
YAMASHITA Tadashi  麻布大学, 獣医学部, 教授 (30220338)
MIZUMOTO Shuji  名城大学, 薬学部, 助教 (40443973)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsコンドロイチン硫酸 / ヒアルロニダーゼ / 加水分解酵素 / ヒアルロン酸 / グリコサミノグリカン / 基質特異性
Outline of Final Research Achievements

The aim of this study was to characterize the amino acid residues responsible for the substrate specificity as well as to elucidate the biological functions of hyaluronidase 4 (HYAL4), which is a chondroitin sulfate-specific hydrolase. A series of HYAL4/other hyaluronidases-chimeric proteins and HYAL4 point mutants have been generated, and their preference for substrates has been investigated. The amino acid residues required for the substrate specificity of HYAL4 have been identified. The expression patterns as well as periods of HYAL4 mRNA have also been analyzed in detail. The relation between some diseases and HYAL4 has been investigated, and high expression of HYAL4 in some metastatic cancer cell lines has been demonstrated. We have also succeeded in the preparation of the targeting vector for generation of Hyal4-deficient mice.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (42 results)

All 2015 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (29 results) (of which Invited: 4 results) Book (3 results) Remarks (4 results)

  • [Journal Article] Catabolism of Chondroitin Sulfate2015

    • Author(s)
      Shuhei Yamada
    • Journal Title

      Cell. Mol. Biol. Lett.

      Volume: 20 Issue: 2 Pages: 196-2212

    • DOI

      10.1515/cmble-2015-0011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human genetic disorders and knockout mice deficient in glycosaminoglycan2014

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, and Kazuyuki Sugahara
    • Journal Title

      BioMed Research International

      Volume: 2014 Pages: 495764-495764

    • DOI

      10.1155/2014/495764

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyaluronidases have strong hydrolytic activity toward chondroitin 4-sulfate comparable to that for hyaluronan2012

    • Author(s)
      Tomoko Honda, Tomoyuki Kaneiwa, Shuji Mizumoto, Kazuyuki Sugahara, and Shuhei Yamada
    • Journal Title

      Biomolecules

      Volume: 2 Issue: 4 Pages: 549-563

    • DOI

      10.3390/biom2040549

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of amino acid residues required for the substrate specificity of human and mouse chondroitin sulfate hydrolase (conventional hyaluronidase-4)2012

    • Author(s)
      Tomoyuki Kaneiwa, Anzu Miyazaki, Ryo Kogawa, Shuji Mizumoto, Kazuyuki Sugahara, and Shuhei Yamada
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Issue: 50 Pages: 42119-42128

    • DOI

      10.1074/jbc.m112.360693

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 新規のコンドロイチン硫酸に特異的な加水分解酵素2012

    • Author(s)
      山田修平
    • Journal Title

      応用糖質科学

      Volume: 2 Pages: 104-110

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] サケ鼻軟骨由来のコンドロイチン硫酸プロテオグリカンの構造解析2015

    • Author(s)
      横井友哉、松崎南美、桝谷晃明、坪井誠、菅原一幸、山田修平
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザインクリエイティブセンター神戸(神戸)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expression Analysis of Hyaluronidases in the Mouse Brain during Development2014

    • Author(s)
      Yuka Oiwa, Shuji Mizumoto, Ryoji Kojima, Tadashi Nagamatsu, Shuhei Yamada
    • Organizer
      oint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research “Integrating Glycoscience from Biology and Chemistry to Medicine”
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expression Analysis of Hyaluronidases in the Mouse Brain during Development2014

    • Author(s)
      Yuka Oiwa, Shuji Mizumoto, Ryoji Kojima, Tadashi Nagamatsu, Shuhei Yamada
    • Organizer
      Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research “Glycans in Neuroscience”
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2014-11-16 – 2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] グリコサミノグリカンの代謝2014

    • Author(s)
      山田 修平
    • Organizer
      第8回東北糖鎖研究会
    • Place of Presentation
      岩手医科大学(矢巾町、岩手)
    • Year and Date
      2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Novel CS-E-Binding Proteins in Mouse Brain That May Be Involved in the Neurite Outgrowth Promoting Mechanism through Chondroitin Sulfate E-Type2014

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, Yusuke Yoshikawa, Shuhei Yamada, and Kosei Takeuchi
    • Organizer
      Gordon Research Conference on Proteoglycans 2014
    • Place of Presentation
      Andover, USA
    • Year and Date
      2014-07-07 – 2014-07-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒトヒアルロニダーゼの基質認識に必要なアミノ酸残基の解析2014

    • Author(s)
      岩月遥奈、水本秀二、金岩知之、菅原一幸、山田修平
    • Organizer
      第60回日本薬学会東海支部総会
    • Place of Presentation
      鈴鹿医療大学(鈴鹿)
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] コンドロイチン硫酸特異的加水分解酵素ヒアルロニダーゼ-4の細胞内局在の解析2014

    • Author(s)
      森本千夏、野村優美子、水本秀二、山田修平
    • Organizer
      第60回日本薬学会東海支部総会
    • Place of Presentation
      鈴鹿医療大学(鈴鹿)
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 発生段階の異なるマウス脳におけるヒアルロニダーゼファミリーメンバーの発現解析2014

    • Author(s)
      大岩友香、水本秀二、小島良二、永松正、山田修平
    • Organizer
      第60回日本薬学会東海支部総会
    • Place of Presentation
      鈴鹿医療大学(鈴鹿)
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] コンドロイチン硫酸代謝におけるヒアルロニダーゼの役割2014

    • Author(s)
      山田修平、本田智子、金岩知之、水本秀二、菅原一幸
    • Organizer
      第46回日本結合組織学会学術大会第61回マトリックス研究会大会合同学術集会
    • Place of Presentation
      ウインク愛知(名古屋)
    • Year and Date
      2014-06-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Integrated neuroglycobiology for proteoglycans and chondroitin sulfate-binding proteins2014

    • 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, Jessica C. F. Kwok
    • Organizer
      International Symposium on Glyco-Neuroscience
    • Place of Presentation
      Awaji
    • Related Report
      2013 Research-status Report
  • [Presentation] 妊娠マウスにおける膵臓ランゲルハンス島のヘパラン硫酸の構造変化2014

    • Author(s)
      松崎南美、西田祐美、高橋巌、那谷耕司、山田修平
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of Hyaluronidases in the Catabolism of Chondroitin Sulfate2014

    • Author(s)
      Shuhei Yamada
    • Organizer
      10th International Symposium on Biochemical Roles of Eukaryotic Cell Surface Macromolecules
    • Place of Presentation
      Kolkata, India
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Mass Preparation of Oligosaccharides with Intestinal Absorption Capacity by Hydrolysis of Chondroitin Sulfate Polysaccharides with Subcritical Water Microreaction System2013

    • Author(s)
      Kazuyuki Sugahara, Shuhei Yamada, Shuji Mizumoto, Keiichiro Matsushima, Haruo Ura, and Nobuyuki Miyamoto
    • Organizer
      13th International Conference of FFC and 1st International Symposium of Academic Society for Functional Foods and Bioactive Compounds
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Research-status Report
  • [Presentation] マイクロ化学プロセスによる新規糖鎖食品の開発2013

    • Author(s)
      松嶋景一郎、浦晴雄、宮本宣之、菅原一幸、山田修平、水本秀二
    • Organizer
      北海道立総合研究機構 技術移転フォーラム2013
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] 第59回日本薬学会東海支部総会2013

    • Author(s)
      山田修平、松嶋景一郎、浦晴雄、宮本宣之、菅原一幸
    • Organizer
      第59回日本薬学会東海支部総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] マイクロ化学プロセスを利用したコンドロイチン硫酸オリゴ糖の大量調製方法の確立2013

    • 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
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトとマウスにおけるコンドロイチン硫酸加水分解酵素の基質特異性の違いに関わるアミノ酸残基の同定2013

    • Author(s)
      山田修平、金岩知之、宮崎杏、古川諒、水本秀二、菅原一幸
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences involved in brain development2013

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, Kittiwan Kalayanamitra, Shuhei Yamada, and Prachya Kongtawelert
    • Organizer
      8th International Conference on Proteoglycans
    • Place of Presentation
      Frankfurt, Germany
    • Related Report
      2013 Research-status Report
  • [Presentation] Studies on the Role of Hyaluronidases in the Catabolism of Chondroitin Sulfate2013

    • Author(s)
      Shuhei Yamada
    • Organizer
      8th International Conference on Proteoglycans
    • Place of Presentation
      Frankfurt, Germany
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] グリコサミノグリカンの生合成・代謝・機能の研究2013

    • Author(s)
      山田修平
    • Organizer
      糖鎖化学中部拠点 第11回「若手の力」フォーラム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ヒアルロニダーゼはコンドロイチン4-硫酸に対しヒアルロン酸と同程度の強い加水分解活性をもつ2013

    • Author(s)
      山田修平、本田智子、金岩知之、水本秀二、菅原一幸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸特異的加水分解酵素の発現組織の解析および精巣における機能の研究2012

    • Author(s)
      古川諒、金岩知之、宮崎杏、菅原一幸、山田修平
    • Organizer
      日本薬学会北海道支部137例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸特異的加水分解酵素ヒアルロニダーゼ-4の酵素活性に必要なアミノ酸残基の同定2012

    • Author(s)
      山田修平、金岩知之、宮崎杏、水本秀二、菅原一幸
    • Organizer
      第58回日本薬学会東海支部 総会・大会
    • Place of Presentation
      静岡
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸特異的加水分解酵素ヒアルロニダーゼ-4の酵素活性に必要なアミノ酸残基の同定2012

    • Author(s)
      金岩知之、宮崎杏、水本秀二、菅原一幸、山田修平
    • Organizer
      第49回日本生化学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸特異的加水分解酵素の発現組織の解析およびその機能の研究2012

    • Author(s)
      古川諒、金岩知之 、宮崎杏、菅原一幸、山田修平
    • Organizer
      第49回日本生化学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトヒアルロニダーゼはコンドロイチン硫酸Aをヒアルロン酸と同程度の速度で加水分解する2012

    • Author(s)
      本田智子、金岩知之、水本秀二、菅原一幸、山田修平
    • Organizer
      第49回日本生化学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸に特異的な加水分解酵素に関する研究2012

    • Author(s)
      山田修平,金岩知之,宮崎杏,古川諒,水本秀二,菅原一幸
    • Organizer
      第31回日本糖質学会年会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトヒアルロニダーゼのコンドロイチン4硫酸に対する高い加水分解活性2012

    • Author(s)
      本田智子、金岩知之、水本秀二、菅原一幸、山田修平
    • Organizer
      第31回日本糖質学会年会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒアルロニダーゼの本来の基質はヒアルロン酸ではなくコンドロイチン硫酸2012

    • Author(s)
      山田修平、本田智子、金岩知之、水本秀二、菅原一幸
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] Biochemical Roles of Eukaryotic Cell Surface Macromolecules2015

    • Author(s)
      Shuhei Yamada
    • Total Pages
      411
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Encyclopedia of Polymeric Nanomaterials2015

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, and Shuhei Yamada
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Adv. Exp. Med. Biol. Vol 749, “Biochemical Roles of Eukaryotic Cell Surface Macromolecules” (Sudhakaran, P. and Surolia, A., eds.)2012

    • Author(s)
      Shuhei Yamada
    • Total Pages
      340
    • Publisher
      Springer, Heidelberg
    • Related Report
      2012 Research-status Report
  • [Remarks] 名城大学薬学部病態生化学

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 名城大学薬学部病態生化学研究室ホームページ

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 名城大学 薬学部 病態生化学研究室

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2012 Research-status Report
  • [Remarks] 名城大学薬学部 > 研究活動 > 研究室紹介 > 病態生化学研究室

    • URL

      http://www-yaku.meijo-u.ac.jp/kenkyu/staff/pathobiochemistry.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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