Comprehensive analysis of glycan metabolic networks by chemical glycomic approach

• Project/Area Number: 18H02565
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kinjo Gakuin University
• Principal Investigator: Shinohara Yasuro 金城学院大学, 薬学部, 教授 (20374192)
• Co-Investigator(Kenkyū-buntansha): 古川 潤一 北海道大学, 医学研究院, 特任准教授 (30374193) ; 吉岡 弘毅 金城学院大学, 薬学部, 助教 (30756606)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: ハイブリッド型 / モノアンテナ型 / パウチマンノース型 / 遊離N-glycan / N-glycan / 定性・定量解析 / 細胞内動態 / グライコミクス / 糖鎖代謝 / 阻害剤 / ブレフェルディンA / ケミカルグライコミクス / 複合糖質 / 遊離オリゴ糖 / スワインソニン / キフネシン / 1-デオキシマンノジリマイシン / 2-フルオロフコース

Outline of Final Research Achievements

Aiming to gain insight into the metabolic pathways of glycan metabolisms of which pathways are poorly understood, we performed gross glycomic analyses upon exposure of HepG2 cells to various glycan metabolism inhibitors of which inhibitory mechanisms are well understood (e.g. inhibitors of alpha-glucosidases, alpha-mannosidases, intracellular protein transport, sarco-endoplasmic reticulum Ca(2+)-ATPases, etc.). These analyses allowed to clarify the correlation between inhibitor employed and expression profile of glycans of which metabolic pathways are not fully understood.

Academic Significance and Societal Importance of the Research Achievements

本研究により糖鎖代謝の阻害メカニズムが多様な多種類の阻害剤について主にN-glycanと遊離N-glycanの代謝経路に与える影響を明らかにした。代謝経路が十分に明らかにされていない複合型・ハイブリッド型の遊離オリゴ糖やパウチマンノース型のN-glycanなどの糖鎖も阻害剤依存的に発現がダイナミックに変動したことからこれらの代謝経路の推定に資する結果が得られた。代謝経路の解明や発現変動の機能解析への展開が期待される。

Research Products

• [Journal Article] Exposure to brefeldin A induces unusual expression of hybrid- and complex-type free N-glycans in HepG2 cells (2023)
  • Author(s): Sugiura Kanako、Kawai Yuho、Yamamoto Arisa、Yoshioka Hiroki、Kiyohara Yuika、Iida Ayaka、Ozawa Yurika、Nishikawa Mai、Miura Nobuaki、Hanamatsu Hisatoshi、Furukawa Jun-ichi、Shinohara Yasuro
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Subjects Volume: 1867 Issue: 5 Pages: 130331-130331
  • DOI: 10.1016/j.bbagen.2023.130331
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of the context of downstream N- and free N-glycomic alterations induced by swainsonine in HepG2 cells (2022)
  • Author(s): Morikawa Chie、Sugiura Kanako、Kondo Keina、Yamamoto Yurie、Kojima Yuma、Ozawa Yurika、Yoshioka Hiroki、Miura Nobuaki、Piao Jinhua、Okada Kazue、Hanamatsu Hisatoshi、Tsuda Masumi、Tanaka Shinya、Furukawa Jun-ichi、Shinohara Yasuro
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Subjects Volume: 1866 Issue: 9 Pages: 130168-130168
  • DOI: 10.1016/j.bbagen.2022.130168
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Toolbox Accelerating Glycomics (TAG): Improving Large-Scale Serum Glycomics and Refinement to Identify SALSA-Modified and Rare Glycans (2022)
  • Author(s): Miura Nobuaki、Hanamatsu Hisatoshi、Yokota Ikuko、Akasaka-Manya Keiko、Manya Hiroshi、Endo Tamao、Shinohara Yasuro、Furukawa Jun-ichi
  • Journal Title: International Journal of Molecular Sciences Volume: 23 Issue: 21 Pages: 13097-13097
  • DOI: 10.3390/ijms232113097
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Toolbox Accelerating Glycomics (TAG): Glycan Annotation from MALDI-TOF MS Spectra and Mapping Expression Variation to Biosynthetic Pathways (2020)
  • Author(s): Miura Nobuaki、Hanamatsu Hisatoshi、Yokota Ikuko、Okada Kazue、Furukawa Jun-Ichi、Shinohara Yasuro
  • Journal Title: Biomolecules Volume: 10 Issue: 10 Pages: 1383-1383
  • DOI: 10.3390/biom10101383
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of the susceptibility of reducing disaccharides composed of d-glucose to glycation using the Maillard reaction and a novel sensitive method that measures the percentage of the open-ring form (2020)
  • Author(s): Yasuro Shinohara, Yurika Ozawa, Akimi Okita, Koichi Kato, Taku Chiba, Nobuaki Miura, Jun-Ichi Furukawa
  • Journal Title: Carbohydrate Research Volume: 493 Pages: 108019-108019
  • DOI: 10.1016/j.carres.2020.108019
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Brefeldin AはHepG2細胞においてユニークなハイブリッド型やコンプレックス型の遊離N-glycanの発現を誘導する (2023)
  • Author(s): 清原 由衣可、杉浦 花菜子、川合 裕穂、山本 有紗、飯田 彩華、小澤 優里香、吉岡 弘毅、篠原 康郎
  • Organizer: 日本薬学会第143年会
• [Presentation] 三浦信明, 花松久寿 ,横田育子, 篠原康郎, 木下聖子, 古川潤一 (2023)
  • Author(s): グライコミクスのプロトコルと 解析ソフトToolbox Accelerating Glycomics (TAG)
  • Organizer: 質量分析インフォマティクス研究会・第8回公開ワークショップ
• [Presentation] スワインソニンにより誘導されるユニークなフコシル化を阻害したときの結合型および遊離型N-glycanの代謝応答 (2022)
  • Author(s): 小澤優里香、杉浦 花菜子、山本 友里恵、森川 智恵、近藤 恵尚、小島 由真、篠原 康郎
  • Organizer: 第68回 日本薬学会東海支部会大会