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Effect of polyamines on the N-glycosylation of antibody and its production.

Research Project

Project/Area Number 18K06652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionTokyo University of Science

Principal Investigator

HIGASHI KYOHEI  東京理科大学, 薬学部薬学科, 講師 (10463829)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords抗体医薬 / ポリアミン / N-結合型糖鎖 / 小胞体ストレス / N型糖鎖 / オリゴ糖転移酵素 / 抗体医薬品 / ポリアミンモジュロン
Outline of Final Research Achievements

Increased level of terminal galactosylation of N-glycan of antibody and decreased level of antibody production were found in polyamine-depleted cells. Thus, the genes whose expression level was enhanced by polyamines (polyamine modulon) were explored, however, it was found that polyamine depletion cause the ER stress because expression levels of BiP, carleticulin were increased in ployamine depleted cells. In addition, B4Gal-T1 level was also elevated in polyamine depleted cells. These results are consisted with the result of ER stress response caused by glucose starvation or tunicamycin treatment. Thus, these results suggest that polyamines influence the biosynthetic pathway of dolichol-linked oligosaccharide (DLO) on the endoplasmic reticulum. The experiments are in progress to identify the polyamine modulon in DLO sythetic pathway.

Academic Significance and Societal Importance of the Research Achievements

糖鎖は細胞の環境や状態に応じてその構造が変化します。そのため、糖鎖を有する抗体医薬を細胞で生産する際には、その培養条件を非常に厳密にコントロールする必要があり、非常にコストがかかります。細胞増殖促進因子ポリアミンは細胞の状態に応じてその量が変化しますが、私達は今回、ポリアミンが抗体の糖鎖構造に影響を及ぼすことを明らかにしました。本研究で得られた成果は、安価で安定した抗体の生産技術の開発に資すると考えています。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (7 results) Remarks (3 results)

  • [Int'l Joint Research] レンセリア工科大学(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] グリコサミノグリカン構造に関連する遺伝子の発現制御機構と生合成過程における ポリアミンの役割2020

    • Author(s)
      Higashi Kyohei
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 32 Issue: 189 Pages: J143-J151

    • DOI

      10.4052/tigg.1979.7j

    • NAID

      130007907496

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways2020

    • Author(s)
      Higashi Kyohei
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 32 Issue: 189 Pages: E167-E175

    • DOI

      10.4052/tigg.1979.7e

    • NAID

      130007907492

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure2020

    • Author(s)
      Ko Kenta、Suzuki Takehiro、Ishikawa Ryota、Hattori Natsuko、Ito Risako、Umehara Kenta、Furihata Tomomi、Dohmae Naoshi、Linhardt Robert J.、Igarashi Kazuei、Toida Toshihiko、Higashi Kyohei
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 52 Pages: 18614-18624

    • DOI

      10.1074/jbc.ra120.015105

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Structural and Compositional Changes of Chondroitin Sulfate Chains in the Aged Mouse Hippocampus2019

    • Author(s)
      SUZUKI YUJI、KEREVER AURELIEN、TANAKA TAKAHIRO、HIGASHI KYOHEI、ARIKAWA-HIRASAWA ERI
    • Journal Title

      Juntendo Medical Journal

      Volume: 65 Issue: 1 Pages: 64-70

    • DOI

      10.14789/jmj.2019.65.JMJ18-OA13

    • NAID

      130007632011

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5′-untraslated region2018

    • Author(s)
      Yamaguchi Katsutoshi、Asakura Kiryu、Imamura Masataka、Kawai Gota、Sakamoto Taiichi、Furihata Tomomi、Linhardt Robert J.、Igarashi Kazuei、Toida Toshihiko、Higashi Kyohei
    • Journal Title

      Biochemical Journal

      Volume: 475 Issue: 23 Pages: 3797-3812

    • DOI

      10.1042/bcj20180672

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GLI1 Inhibitors Identified by Target Protein Oriented Natural Products Isolation (TPO-NAPI) with Hedgehog Inhibition2018

    • Author(s)
      Arai Midori A.、Ochi Fumie、Makita Yoshinori、Chiba Tetsuhiro、Higashi Kyohei、Suganami Akiko、Tamura Yutaka、Toida Toshihiko、Iwama Atsushi、Sadhu Samir K.、Ahmed Firoj、Ishibashi Masami
    • Journal Title

      ACS Chemical Biology

      Volume: 13 Issue: 9 Pages: 2551-2559

    • DOI

      10.1021/acschembio.8b00492

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protective Effects of Brain Infarction by N -Acetylcysteine Derivatives2018

    • Author(s)
      Uemura Takeshi、Watanabe Kenta、Ko Kenta、Higashi Kyohei、Kogure Noriyuki、Kitajima Mariko、Takayama Hiromitsu、Takao Koichi、Sugita Yoshiaki、Sakamoto Akihiko、Terui Yusuke、Toida Toshihiko、Kashiwagi Keiko、Igarashi Kazuei
    • Journal Title

      Stroke

      Volume: 49 Issue: 7 Pages: 1727-1733

    • DOI

      10.1161/strokeaha.118.021755

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduction of Spermidine Content Resulting from Inactivation of Two Arginine Decarboxylases Increases Biofilm Formation in Synechocystis sp. PCC 68032018

    • Author(s)
      Kota Kera, Tatsuya Nagayama, Kei Nanatani, Chika Saeki-Yamoto, Akira Tominaga, Satoshi Souma, Nozomi Miura, Kota Takeda, Syunsuke Kayamori, Eiji Ando, Kyohei Higashi, Kazuei Igarashi and Nobuyuki Uozumi
    • Journal Title

      Journal of Bacteriology

      Volume: 9 Issue: 9 Pages: 664-706

    • DOI

      10.1128/jb.00664-17

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ポリアミンによるヘパラン硫酸伸長酵素EXT1の発現調節機構2021

    • Author(s)
      鈴木雅斗、浅見詩生、工藤遥、今村正隆、河合剛太、五十嵐一衛、戸井田敏彦、東恭平
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗IL-8抗体の糖鎖構造に対する細胞増殖促進因子ポリアミンの影響2020

    • Author(s)
      真中 瞳、本田 達也、浅見 詩生、五十嵐 一衛、戸井田 敏彦、東 恭平
    • Organizer
      日本ポリアミン学会 第11回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗IL-8抗体の糖鎖構造に対する細胞増殖促進因子ポリアミンの影響2019

    • Author(s)
      真中瞳、本田達也、浅見詩生、五十嵐一衛、戸井田敏彦、東恭平
    • Organizer
      第32回バイオメディカル分析科学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳梗塞急性期におけるヘパラン硫酸分解機構の解明2019

    • Author(s)
      高 健太、東 恭平、服部 奈津子、石川 涼太、梅原 健太、降幡 知巳、五十嵐 一衛、戸井田 敏彦
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] メチレンブルーを用いたグリコサミノグリカンの半定量法の開発2018

    • Author(s)
      岡本 悠佑、東 恭平、戸井田 敏彦
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ポリアミンによるEXT1のタンパク質合成促進機構の解明2018

    • Author(s)
      浅見 詩生、 東 恭平、工藤 遥香、五十嵐 一衛、戸井田 敏彦
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ポリアミンによるEXT1のタンパク質合成促進機構の解明2018

    • Author(s)
      浅見 詩生、東 恭平、工藤 遥香、今村 正隆、西村 和洋、五十嵐 一衛、戸井田 敏彦
    • Organizer
      東京慈恵会医科大学 学外共同研究助成 ポリアミンと核酸の共進化 第17回 合同シンポジウム
    • Related Report
      2018 Research-status Report
  • [Remarks] 東京理科大学 研究者情報データベース

    • URL

      https://www.tus.ac.jp/academics/teacher/p/index.php?7015

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東 恭平|論文・著書・学会発表・特許|東京理科大学

    • URL

      https://www.tus.ac.jp/fac_grad/p/achievement.php?7015

    • Related Report
      2019 Research-status Report
  • [Remarks] 東恭平_教員プロフィール_東京理科大学

    • URL

      https://www.tus.ac.jp/fac_grad/p/index.php?7015

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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