Identification of novel proteins that bind to various immunosuppressive / immunomodulatory drugs and clinical implications in the immune system

• Project/Area Number: 15K09516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Akita University
• Principal Investigator: WAKUI Hideki 秋田大学, 理工学研究科, 教授 (70240463)
• Co-Investigator(Kenkyū-buntansha): 布村 渉 秋田大学, 理工学研究科, 准教授 (70256478) ; 小松田 敦 秋田大学, 医学(系)研究科(研究院), 准教授 (70272044)
• Research Collaborator: DOHMAE Naoshi ; ODAKA Masafumi ; MSTSUMURA Hirotoshi ; OMOKAWA Ayumi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 免疫抑制剤・免疫調節剤 / 薬剤アフィニティークロマトグラフィー / ヒト血液 / 動物臓器 / 薬剤結合蛋白質（標的蛋白質候補） / 新規薬理作用 / 臨床応用 / 温故知新創薬 / 免疫抑制剤 / 免疫調節剤 / 血液・免疫組織 / 薬剤標的蛋白質 / 薬剤アフィニティーカラム

Outline of Final Research Achievements

Clinical effectiveness and safely of widely used immunosuppressive / immunomodulatory drugs have been confirmed. Since these drugs are generally cheap, it is an important clinical issue to reassess their pharmacological actions from a pharmacoeconomical point of view.
In this study, several drugs widely used in the treatment of autoimmune diseases, such as rheumatoid arthritis, and allergic diseases are selected. Novel drug-binding proteins having important roles in the immune response processes (candidates for drug-target proteins) were identified. The results suggest novel pharmacological actions of these drugs and their clinical applications in the feature.

Research Products

• [Journal Article] Hydroxychloroquine binding to cytoplasmic domain of Band 3 in human erythrocytes: Novel mechanistic insights into drug structure, efficacy and toxicity. (2016)
  • Author(s): Nakagawa M, Sugawara K, Goto T, Wakui H, Nunomura W.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 473 Issue: 4 Pages: 999-1004
  • DOI: 10.1016/j.bbrc.2016.04.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enzymatic and thermodynamic profiles of a heterotetramer lactate dehydrogenase isozyme in swine. (2016)
  • Author(s): Goto, T., Sugawara, K., Nakamura, S., Kidokoro, S., Wakui, H., & Nunomura, W.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 474 Issue: 4 Pages: 860-867
  • DOI: 10.1016/j.bbrc.2016.09.118
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] メトトレキサート新規標的タンパク質としてのマクロファージ遊走阻害因子の同定と構造機能解析 (2017)
  • Author(s): 松村洋寿, 杉島小雪, 面川歩, 布村渉, 堂前直, 尾高雅文, 廣川誠, 涌井秀樹
  • Organizer: 第44回生体分子科学討論会
• [Presentation] リウマチ薬メトトレキサート新規標的タンパク質としてのマクロファージ遊走阻害因子との相互作用解析 (2017)
  • Author(s): 杉島小雪, 松村洋寿, 面川歩, 布村渉, 堂前直, 尾高雅文, 廣川誠, 涌井秀樹
  • Organizer: 第44回生体分子科学討論会
• [Presentation] トトレキサート新規標的タンパク質マクロファージ遊走阻害因子の構造機能解析 (2017)
  • Author(s): 松村洋寿, 杉島小雪, 面川歩, 布村渉, 堂前直, 尾高雅文, 廣川誠, 涌井秀樹
  • Organizer: 第11回バイオ関連化学シンポジウム
• [Presentation] 抗リウマチ薬メトトレキサートとMIFサイトカインファミリータンパク質の相互作用解析 (2017)
  • Author(s): 杉島小雪, 松村洋寿, 面川歩, 布村渉, 堂前直, 尾高雅文, 廣川誠, 涌井秀樹
  • Organizer: 第11回バイオ関連化学シンポジウム
• [Presentation] リウマチ薬メトトレキサート新規標的タンパク質としてのマクロファージ遊走阻害因子の機能及び相互作用解析 (2017)
  • Author(s): 杉島小雪, 松村洋寿, 面川歩, 尾高雅文, 廣川誠, 涌井秀樹
  • Organizer: 第69回日本生物工学学会大会
• [Presentation] Conserved and unique enzymatic and thermodynamic properties of lactate dehydrogenase in skeletal muscle of ectothermic, mesothermic and endothermic vertebrates (2016)
  • Author(s): Goto T, Nakagawa M, Sugawara K, Takahashi T, Yonezawa M, Wakui H, Nunomura W
  • Organizer: The 22nd International Congress of Zoology
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Inhibition of heterotetramer lactate dehydrogenase isozyme blocked cell proliferation of K562 (2016)
  • Author(s): Goto T, Sugawara K, Asanuma K, Ubukawa K, Guo Y, Kobayashi I, Takahashi N, Wakui H, Nunomura W
  • Organizer: The 12th International Congress of Cell Biology
  • Place of Presentation: プラハ（チェコ共和国）
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] ヒドロキシクロロキンを用いた乳酸脱水素酵素の活性阻害による細胞増殖抑制 (2016)
  • Author(s): 後藤樹史，菅原琴美，浅沼研，中川瑞希，小林五十鈴，鵜生川久美，山下順助，髙橋直人，澤田賢一，涌井秀樹，布村渉
  • Organizer: 第68回日本細胞生物学会大会/日本ケミカルバイオロジー学会第11回年会/合同大会
  • Place of Presentation: 京都テレサ（京都府京都市）
  • Year and Date: 2016-06-15
• [Presentation] Inhibition of lactate dehydrogenase isozymes blocked cell proliferation. (2015)
  • Author(s): Goto T, Sugawara K, Nakagawa M, Kobayashi I, Ubukawa K, Asanuma K, Yamashita J, Sawada K, Wakui H, Nunomura W.
  • Organizer: American Society for Cell Biology 2015 Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-12-14
  • Int'l Joint Research
• [Remarks] 秋田大学理工学部生命科学科疾患生物学研究室ホームページ
  • URL: http://www.gipc.akita-u.ac.jp/~wakui517/index.htm