Study on the structure and functions of sulfated glycosaminoglycans involved in the development or treatment of liver diseases.

• Project/Area Number: 19590052
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: YAMADA Shuhei Hokkaido University, 大学院・先端生命科学研究院, 准教授 (70240017)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: グリコサミノグリカン / コンドロイチン硫酸 / ヘパラン硫酸 / 肝再生 / C型肝炎ウイルス / 細胞増殖因子 / サイトカイン / C型肝炎ウィルス

Research Abstract

硫酸化グリコサミノグリカン(GAG)は細胞増殖因子など様々な生理活性タンパク質と特異的に相互作用し、それらの活性を調節する。また、ウィルス感染の過程においても極めて重要な役割を果たしている。本研究では、再生期間の異なる再生肝よりGAG を精製し、その構造変化と機能変化を解析した。また、様々なGAG について、C 型肝炎ウィルスの感染への影響を検討した。さらにGAG の構造解析を行うための新規の技術や酵素を開発した。

Research Products

• [Journal Article] Isolation and Characterization of a Novel Chondroitin Sulfate from Squid Liver Integument Rich in N-Acetylgalactosamine(4,6-O-disulfate) and Glucuronate(3-O-sulfate) Residues (2009)
  • Author(s): Ajaya Kumar Shetty, Takanari Kobayashi, Shuji Mizumoto, Masaki Narumi, Yoshiaki Kudo, Shuhei Yamada, and Kazuyuki Sugahara
  • Journal Title: Carbohydr. Res. (in press)
  • Peer Reviewed
• [Journal Article] Structural and Functional Changes of Sulfated Glycosaminoglycans in Xenopus laevis during Embryogenesis (2009)
  • Author(s): Shuhei Yamada, Masako Onishi, Reiko Fujinawa, Yuko Tadokoro, Koji Okabayashi, Makoto Asashima, and Kazuyuki Sugahara,
  • Journal Title: Glycobiology (in press)
  • Peer Reviewed
• [Journal Article] Structural and Functional Changes of Sulfated Glycosaminoglycans in Xenopus laevis during Embryogenesis (2009)
  • Author(s): Shuhei Yamada
  • Journal Title: Glycobiology (in press)
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a novel chondroitin sulfate from squid liver integument rich in N-acetvlaalactosamine (4.6-O-disulfate) and alucuronate(3-O-sulfatel) residues (2009)
  • Author(s): Ajaya Kumar Shetty
  • Journal Title: Carbohydrate Research (in press)
  • Peer Reviewed
• [Journal Article] Identificationof a Novel Chondroitin Hydrolase inCaenorhabditis elegans. These authorscontributed equally to the work (2008)
  • Author(s): Tomoyuki Kaneiwa, Shuhei Yamada, Shuji Mizumoto, Adriana M. Montano, Souhei Mitani and Kazuyuki Sugahara
  • Journal Title: J. Biol. Chem. 283 Pages: 14971-14979
  • Peer Reviewed
• [Journal Article] Potential Therapeutic Application ofChondroitin Sulfate/Dermatan Sulfate (2008)
  • Author(s): Shuhei Yamada and Kazuyuki Sugahara
  • Journal Title: Current Drug Discovery Technologies 5 Pages: 289-301
  • Peer Reviewed
• [Journal Article] Determination ofIduronic Acid and Glucuronic Acid in SulfatedChondroitin/Dermatan Hybrid Chains by1H-Nuclear Magnetic Resonance Spectroscopy.*These authors contributed equally to the work. (2008)
  • Author(s): Fuchuan Li, Shuhei Yamada, Basappa, Ajaya K. Shetty, Makiko Sugiura, and Kazuyuki Sugahara
  • Journal Title: Glycoconjugate J. 25 Pages: 603-610
  • Peer Reviewed
• [Journal Article] Determination of Iduronic Acid and Glucuronic Acid in Sulfated Chondroitin/Dermatan Hybrid Chains by ^1H-Nuclear Magnetic Resonance Spectroscopy (2008)
  • Author(s): Fuchuan Li
  • Journal Title: Glycoconjugate J. 25 Pages: 603-610
  • Peer Reviewed
• [Journal Article] Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate (2008)
  • Author(s): Shuhei Yamada
  • Journal Title: Current Drug Discovery Technologies 5 Pages: 289-301
  • Peer Reviewed
• [Journal Article] Identification of a Novel Chondroitin Hydrolase in Caenorhabditis elegans (2008)
  • Author(s): Tomoyuki Kaneiwa
  • Journal Title: J. Biol. Chem. 283 Pages: 14971-14979
  • Peer Reviewed
• [Journal Article] Determination of Iduronic Acid and Glucuronic Acid in Sulfated Chondroitin/Dermatan Hybrid Chains by 1H-Nuclear Magnetic Resonance Spectroscopy (2008)
  • Author(s): Fuchuan Li
  • Journal Title: Glycoconjugate J. (in press)
  • Peer Reviewed
• [Journal Article] Chondroitinase-mediatedDegradation of Rare 3-O-Sulfated GlucuronicAcid in Functional Oversulfated Chondroitin Sulfate K and E. (2007)
  • Author(s): Duriya Fongmoon, Ajaya Kumar Shetty, Basappa, Shuhei Yamada, Makiko Sugiura,Prachya Kongtawelert, and Kazuyuki Sugahara
  • Journal Title: J. Biol. Chem. 282 Pages: 36895-36904
  • Peer Reviewed
• [Journal Article] Glycosaminoglycans in Hydra magnipapillata(Hydrozoa, Cnidaria) : Demonstration ofChondroitin in the Developing Nematocyst,Sting Organelle, and Structural Characterization of Glycosaminoglycans (2007)
  • Author(s): Shuhei Yamada, Hideto Morimoto, ToshitakaFujisawa, and Kazuyuki Sugahara
  • Journal Title: Glycobiology 17 Pages: 886-894
  • Peer Reviewed
• [Journal Article] StructuralDetermination of Novel SulfatedOctasaccharides Isolated from ChondroitinSulfate of Shark Cartilage and TheirApplication for Characterizing MonoclonalAntibody Epitopes. (2007)
  • Author(s): Sarama S. Deepa, Shuhei Yamada, Shigeyuki Fukui, and Kazuyuki Sugahara
  • Journal Title: Glycobiology 17 Pages: 631-645
  • Peer Reviewed
• [Journal Article] Structural determination of novel sulfated octasaccharides isolated from chondroitin sulfate of shark cartilage and their application for characterizing monoclonal antibody epitopes. (2007)
  • Author(s): Sarama S. Deepa
  • Journal Title: Glycobiology 17 Pages: 631-645
  • Peer Reviewed
• [Journal Article] Glycosaminoglycans in Hydra magnipapillata(Hydrozoa, Cnidaria): demonstration of chondroitin in the developing nematocyst, sting organelle, and structural characterization of glycosaminoglycans. (2007)
  • Author(s): Shuhei Yamada
  • Journal Title: Glycobiology 17 Pages: 886-894
  • Peer Reviewed
• [Journal Article] Chondroitinase-mediated Degradation of Rare 3-Ο-Sulfated Glucuronic Acid in Functional Oversulfated Chondroitin Sulfate K and E. (2007)
  • Author(s): Duriya Fongmoon
  • Journal Title: J. Biol. Chem. 282 Pages: 36895-36904
  • Peer Reviewed
• [Presentation] Structural analysis ofchondroitin sulfate and dermatansulfate in heparan sulfate glucuronylC5-epimerase-deficient mice、BMB2008 (2008)
  • Author(s): 山田修平
  • Organizer: 第81回日本生化学会大会・第31回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 硫酸化グリコサミノグリカンとC型肝炎ウイルスのエンベロープタンパク質との相互作用の解析 (2008)
  • Author(s): 小林芙美
  • Organizer: BMB2008(第81回日本生化学会大会・第31回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 硫酸化グリコサミノグリカンとC型肝炎ウイルスのエンベロープタンパク質との相互作用の解析 (2008)
  • Author(s): 小林芙美
  • Organizer: BMB2008(第81回日本生化学会大会・第31回日本分子生物学会年会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Structural analysis of chondroitin sulfate and dermatan sulfate in henaran sulfate glucuronyl C5-enimerase-deficient mice (2008)
  • Author(s): 山田修平
  • Organizer: BMB2008(第81回日本生化学会大会・第31回日本分子生物学会年会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] C型肝炎ウイルスのエンベロープタンパク質と硫酸化グリコサミノグリカンとの相互作用解析 (2008)
  • Author(s): 小林芙美
  • Organizer: シオノギイノベーションフェアー2008
  • Place of Presentation: 札幌
  • Year and Date: 2008-08-28
• [Presentation] C型肝炎ウイルスのエンベロープタンパク質と硫酸化グリコサミノグリカンとの相互作用解析 (2008)
  • Author(s): 小林芙美
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-20
• [Presentation] 線虫Caenorhabditis elegansのコンドロイチン加水分解酵素による主要な分解産物の構造解析 (2008)
  • Author(s): 金岩知之
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-20
• [Presentation] 組換え体ヒトヒアルロニダーゼ-1および-2の基質特異性の研究 (2008)
  • Author(s): 山田修平
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-20
• [Presentation] イカ肝臓外皮由来のコンドロイチン硫酸の構造および生理活性の解析 (2008)
  • Author(s): 小林孝成
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 組換え体ヒトヒアルロニダーゼ-4 の基質特異性の研究 (2008)
  • Author(s): 山田修平
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 線虫Caenorhabditis elegansにおける新規のコンドロイチン加水分解酵素の同定 (2008)
  • Author(s): 山田修平
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 組換え体ヒトピアルロニダーゼ-4の基質特異性の研究 (2008)
  • Author(s): 山田修平
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 組換え体ヒトピアルロニダーゼ-1および-2の基質特異性の研究 (2008)
  • Author(s): 山田修平
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] イカ肝臓外皮由来のコンドロイチン硫酸の構造と神経突起伸長促進活性 (2008)
  • Author(s): 小林孝成
  • Organizer: 日本生化学会北海道支部第45 回例会
  • Place of Presentation: 札幌
  • Year and Date: 2008-08-08
• [Presentation] 線虫Caenorhabditis elegansにおける新規のコンドロイチン加水分解酵素の同定 (2008)
  • Author(s): 山田修平
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Presentation] 線虫Caenorhabditis elegansにおける新規のコンドロイチン加水分解酵素の同定 (2008)
  • Author(s): 金岩知之
  • Organizer: 第42回高分子学会北海道支部研究発表会
  • Place of Presentation: 札幌
  • Year and Date: 2008-01-29
• [Presentation] Chondroitinase-MediatedDegradation of Rare 3-O-SulfatedGlucuronic Acid in Functional OversulfatedChondroitin Sulfate Chains (2007)
  • Author(s): Ajaya K. Shetty
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] コンドロイチン硫酸(CS)/デルマタン硫酸(DS)中のグルクロン酸(GlcA)とイズロン酸(IdoA)の1H NMR解析による定量 (2007)
  • Author(s): 李福川
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Chondroitinase-Mediated Degradation of Rare 3-Ο-Sulfated Glucuronic Acid in Functional Oversulfated Chondroitin Sulfate Chains (2007)
  • Author(s): Ajaya K Shetty
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 単クローン抗体MO-225 が認識するコンドロイチン硫酸E由来のオリゴ糖の構造解析 (2007)
  • Author(s): 山田修平
  • Organizer: 第27回日本糖質学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-03
• [Presentation] サメ軟骨コンドロイチン硫酸由来の八糖の構造解析と抗体のエピトープ解析への応用 (2007)
  • Author(s): 山田修平
  • Organizer: 第27回日本糖質学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-03
• [Presentation] 単クローン抗体MO-225が認識するコンドロイチン硫酸E由来のオリゴ糖の構造解析 (2007)
  • Author(s): Sarama Sathyaseelan Deepa
  • Organizer: 第27回日本糖質学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-03
• [Presentation] 抗コンドロイチン硫酸抗体のエピトープ構造 (2007)
  • Author(s): 菅原一幸
  • Organizer: 第27回日本糖質学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-01
• [Presentation] Chondroitinase-Mediated Degradation ofRare 3-O-Sulfated Glucuronic acid inFunctional Oversulfated Chondroitin SulfateChains (2007)
  • Author(s): Duriya Fongmoon
  • Organizer: Glyco19(XIX InternationalSymposium on Glycoconjugates)
  • Place of Presentation: Cairns
  • Year and Date: 2007-07-16
• [Presentation] Chondroitinase-Mediated Degradation of Rare 3-Ο-Sulfated Glucuronic acid in Functional Oversulfated Chondroitin Sulfate Chains. (2007)
  • Author(s): D. Fongmoon
  • Organizer: Glycol9(XIX International Symposium on Glycoconjugates)
  • Place of Presentation: Cairns
  • Year and Date: 2007-07-16
• [Presentation] 抗コンドロイチン硫酸D(CS-D)抗体MO-225が認識するCS-E由来のオリゴ糖の構造解析 (2007)
  • Author(s): 山田修平
  • Organizer: 第44回日本生化学会北海道支部例会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-06
• [Presentation] 抗コンドロイチン硫酸D(CS-D)抗体MO-225が認識するCS-E由来のオリゴ糖の構造解析 (2007)
  • Author(s): Sarama Sathyaseelan Deepa
  • Organizer: 第44回 日本生化学会北海道支部例会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-06
• [Presentation] コンドロイチン硫酸(CS)/デルマタン硫酸(DS)中のグルクロン酸(GlcA)とイズロン酸(IdoA)の1HNMR解析による定量 (2004)
  • Author(s): 山田修平
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
  • Place of Presentation: 横浜
  • Year and Date: 2004-12-12
• [Book] Springer, Tokyo (2008)
  • Author(s): Kazuyuki Sugahara and Shuhei Yamada
  • Publisher: Experimental Glycoscience Glycochemistry,
• [Book] Experimental Glycoscience Glycochemistry (2008)
  • Author(s): Kazuyuki Sugahara
  • Publisher: Springer, Tokyo
• [Patent(Industrial Property Rights)] ムコ多糖分解促進剤 (2007)
  • Inventor(s): 菅原一幸, 山田修平, 水本秀二
  • Industrial Property Rights Holder: 北海道大学
  • Filing Date: 2007-11-09
• [Patent(Industrial Property Rights)] ムコ多糖分解促進剤 (2007)
  • Inventor(s): 菅原一幸, 山田修平, 水本秀二
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 2007-291424
  • Filing Date: 2007-11-09