Elucidation of activation mechanisms for ganglioside-deficient glial cells

• Project/Area Number: 23790361
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: OHMI Yuhsuke 名古屋大学, 医学系研究科, 特任助教 (10584758)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: アストロサイト / ミクログリア / ニューロン / ガングリオシド / 神経変性 / 炎症 / グリア / アストログリア / ミクロドメイン

Research Abstract

Gangliosides (acidic glycosphingolipids) expressed on the plasma membrane are highly expressed in nerve tissues of vertebrates, and are involved in their development and functions. Our study clarified that glial cells components of nerve tissues, also express gangliosides on the plasma membrane, and glial cells in gangliosides-deficient mice were abnormally activated in the brain and enhanced sensitivity for inflammatory cytokines.

Research Products

• [Journal Article] Essential Roles of Gangliosides in the Formation and Maintenance of Membrane Microdomains in Brain Tissues (2012)
  • Author(s): Yuhsuke Ohmi, Yuki Ohkawa, Yoshio Yamauchi, Orie Tajima, Keiko Furukawa, Koichi Furukawa
  • Journal Title: Neurochem Res Volume: 37(6) Pages: 1185-91
  • Peer Reviewed
• [Journal Article] C9-R95X Polymorphism in Patients with Neovascular Age-Related Macular Degeneration (2012)
  • Author(s): Koji Nishiguchi, Tetsuhiro Yasuma, Daisuke Tomida, Makoto Nakamura, Kohei Ishikawa, Masato Kikuchi, Yuhsuke Ohmi, Toshimitsu Niwa, Nobuyuki Hamajima, Koichi Furukawa, and Hiroko Terasaki
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(1) Pages: 508-12
  • Peer Reviewed
• [Journal Article] Disialyl gangliosides enhance tumor phenotypes with differential modalities. (2012)
  • Author(s): Koichi Furukawa
  • Journal Title: Glycqconjugate journal Volume: 29 Issue: 8-9 Pages: 579-584
  • DOI: 10.1007/s10719-012-9423-0
  • Peer Reviewed
• [Journal Article] Fine tuning of cell signals by glycosylation (2012)
  • Author(s): Furukawa K, Ohkawa Y, Yamauchi Y, Hamamura K, Ohmi Y, Furukawa K.
  • Journal Title: J Biochem. Volume: 151 Issue: 6 Pages: 573-578
  • DOI: 10.1093/jb/mvs043
  • NAID: 10031166098
  • Peer Reviewed
• [Journal Article] Essential roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues. (2012)
  • Author(s): Yuhsuke Ohmi
  • Journal Title: Neurochemical Research Volume: 37 Issue: 6 Pages: 1185-1191
  • DOI: 10.1007/s11064-012-0764-7
  • Peer Reviewed
• [Journal Article] Molecular mechanisms for the regulation of nervous systems with glycosphingolipids (2011)
  • Author(s): Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Noriyo Tokuda, Orie Tajima, Keiko Furukawa
  • Journal Title: Seikagaku Volume: 83(3) Pages: 169-173
  • NAID: 10029067618
  • Peer Reviewed
• [Journal Article] Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling (2011)
  • Author(s): Yuki Ohkawa, Yuhsuke Ohmi, Orie Tajima, Yoshio Yamauchi, Keiko Furukawa, Koichi Furukawa
  • Journal Title: Biochem Biophys Res Commun Volume: 411(3) Pages: 483-489
  • Peer Reviewed
• [Journal Article] Regulatory mechanisms of nervous systems with glycosphingolipids (2011)
  • Author(s): Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Noriyo Tokuda, Yuji Kondo, Orie Tajima, Keiko Furukawa
  • Journal Title: Neurochemical Research Volume: 36(9) Pages: 1578-1586
  • Peer Reviewed
• [Journal Article] Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: elucidation by a series of ganglioside-deficient mutant mice (2011)
  • Author(s): Yuhsuke Ohmi, Orie Tajima, Yuki Ohkawa, Yoshio Yamauchi, Yasuo Sugiura, Keiko Furukawa, Koichi Furukawa
  • Journal Title: J Neurochem Volume: 116(5) Pages: 926-935
  • Peer Reviewed
• [Journal Article] O-Linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions. (2011)
  • Author(s): Sakaidani Y, Nomura T, Matsuura A, Ito M, Suzuki E, Murakami K, Nadano D, Matsuda T, Furukawa K, Okajima T
  • Journal Title: Nat Commun. Volume: 13(2) Issue: 1 Pages: 583-583
  • DOI: 10.1038/ncomms1591
  • Peer Reviewed
• [Journal Article] Efficient generation of useful monoclonal antibodies reactive with globotriaosylceramide using knockout mice lacking Gb3/CD77 synthase. (2011)
  • Author(s): Kondo Y.
  • Journal Title: Glycoconj J. Volume: 28 Issue: 6 Pages: 371-384
  • DOI: 10.1007/s10719-011-9335-4
  • Peer Reviewed
• [Journal Article] Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling : induction of the lipgenic pathway by a melanoma antigen (2011)
  • Author(s): Yamauchi Y, Furukawa K, Hamamura K, Furukawa K.
  • Journal Title: Cancer Res. Volume: 71 Issue: 14 Pages: 4989-4997
  • DOI: 10.1158/0008-5472.can-10-4108
  • Peer Reviewed
• [Journal Article] Functional activation of Src family kinase Yes is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3 (2011)
  • Author(s): Hamamura, K., Tsuji, M., Hotta, H., Ohkawa, Y., Takahashi, M., Shibuya, H., Nakashima, H., Yamauchi, Y., Hashimoto, N., Hattori, H., Ueda, M., Furukawa, K., Furukawa. K
  • Journal Title: J.Biol.Chem. Volume: 286 Issue: 21 Pages: 18526-37
  • DOI: 10.1074/jbc.m110.164798
  • Peer Reviewed
• [Presentation] Roles of gangliosides in the regulation of lipid rafts (2013)
  • Author(s): Yuhsuke Ohmi
  • Organizer: The 5thNagoya Global Retreat
  • Place of Presentation: Obu, Aichi
• [Presentation] 脳内環境におけるガングリオシド糖鎖の分別的役割の解明 (2013)
  • Author(s): 大海雄介
  • Organizer: 新学術領域研究「脳内環境:恒常性維持機構とその破綻」冬の班会議
  • Place of Presentation: 京都
• [Presentation] Roles of gangliosides in the regulation of lipid rafts. (2013)
  • Author(s): Yuhsuke Ohmi
  • Organizer: The 5th Nagoya Global Retreat
  • Place of Presentation: あいち健康プラザ（名古屋市）
• [Presentation] 脳内環境におけるガングリオシド糖鎖の分別的役割の解明 (2013)
  • Author(s): 大海雄介
  • Organizer: 新学術領域研究「脳内環境：恒常性維持機構とその破綻」冬の班会議
  • Place of Presentation: 京都大学（京都市）
• [Presentation] 脳内環境におけるガングリオシド糖鎖の分別的役割の解明 (2012)
  • Author(s): 大海雄介
  • Organizer: 新学術領域研究「脳内環境:恒常性維持機構とその破綻」夏のワークショップ
  • Place of Presentation: 仙台
• [Presentation] GM3 only マウスの中枢神経系で高度発現するPerilipin4 はミクログリアに発現しリソゾーム機能を亢進させる (2012)
  • Author(s): 大川祐樹、大海雄介 他
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: マリンメッセ福岡（福岡市）
• [Presentation] ガングリオシド欠損に伴うグリア細胞の機能変異の解析 (2012)
  • Author(s): 大平拡、大海雄介 他
  • Organizer: 糖鎖科学中部拠点 第10回「若手の力」フォーラム
  • Place of Presentation: 静岡県立大学（静岡市）
• [Presentation] 脳内環境におけるガングリオシド糖鎖の分別的役割の解明 (2012)
  • Author(s): 大海雄介
  • Organizer: 新学術領域研究「脳内環境：恒常性維持機構とその破綻」夏のワークショップ
  • Place of Presentation: TKPガーデンシティ仙台（仙台）
• [Presentation] ガングリオシドは神経炎症と変性の抑制に必須である (2011)
  • Author(s): 大海雄介
  • Organizer: 第9回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 名古屋
• [Presentation] Roles of gangliosides on the maintenance of integrity of lipid rafts (2011)
  • Author(s): 大海雄介、田島織絵、大川祐樹、山内祥生、古川圭子、古川 鋼一
  • Organizer: 第84回日本生化学会大会合同大会
  • Place of Presentation: 京都
• [Presentation] Essential roles of gangliosides in the protection of inflammation and neurodegeneration via the regulation of lipid rafts: elucidation by a series of gangliosidedeficient mice. (2011)
  • Author(s): K. Furukawa, Y. Ohmi, O. Tajima, Y. Ohkawa, Y. Yamauchi, K. Furukawa
  • Organizer: 21st International Synposium on Glycoconjugates
  • Place of Presentation: Vienna, Austria
• [Presentation] Regulatory mechanisms of malignant phenotypes of human cancers by tumor-associated carbohydrate antigens in the microdomains. (2011)
  • Author(s): Koichi Furukawa, Kazunori Hamamura, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Ohmi,Yoshio Yamauchi, Keiko Furukawa:
  • Organizer: The 31st Naito Conference on Glycan Expression and Regulation[II]:Metabolites, Stress Response, Microdomains, and Beyond
  • Place of Presentation: Sapporo, Japan
• [Presentation] ガングリオシドは神経炎症と変性の抑制に必須である。 (2011)
  • Author(s): 大海雄介
  • Organizer: 第9回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 名古屋
• [Book] 神経疾患と糖鎖の関わり (2013)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、古川圭子、田島織絵
  • Publisher: Annual Review 神経 2013(株)中外医学
• [Book] 神経疾患と糖鎖の関わり、糖鎖と神経疾患、Annual Review神経 2013 (2013)
  • Author(s): 古川鋼一、大海雄介 他
  • Publisher: 中外医学
• [Book] 糖鎖修飾によるシグナル伝達の制御 (2012)
  • Author(s): 古川鋼一、浜村和紀、大川祐樹、大海雄介、古川圭子
  • Publisher: 実験医学増刊 30(5)「シグナル伝達研究最前線 2012 編集:井上純一郎、武川睦寛、徳永文稔、今井浩三 翻訳後修飾,解析技術,疾患との連関から創薬応用まで」
• [Book] GM3 合成酵素欠損症 (2012)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、徳田典代、古川圭子
  • Publisher: 日本臨床 別冊 新領域別症候群シリーズ 20「先天代謝異常症候群」
• [Book] 糖鎖修飾によるシグナル伝達の制御、実験医学増刊30（5）「シグナル伝達研究最前線2012」 (2012)
  • Author(s): 古川鋼一、大海雄介 他
  • Publisher: 羊土社
• [Book] 別冊 新領域別症候群シリーズ20「先天代謝異常症候群」 (2012)
  • Author(s): 古川鋼一、大海雄介 他
  • Publisher: 日本臨床社
• [Book] 脂質糖鎖による脳神経系統御の分子メカニズム (2011)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、徳田典代、古川圭子
  • Publisher: 生化学
• [Book] 生物機能モデルと新しいリソース・リサーチツール. 第三章 糖鎖関連遺伝子ノックアウトマウス (2011)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、徳田典代、田島織絵、古川圭子
  • Publisher: エル・アイ・シー
• [Book] ガングリオシド欠損と神経機能障害、「脳 21」 (2011)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、徳田典代、田島織絵、古川圭子
  • Publisher: 金芳堂
• [Book] ガングリオシド合成酵素, 糖鎖関連遺伝子ノックアウトマウス シリーズ モデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、徳田典代、田島織絵、古川圭子
  • Publisher: エル・アイ・シー