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Functional analysis of ApoA-I/HDL binding protein for the treatment of atherosclerosis

Research Project

Project/Area Number 20H04124
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionOsaka Medical and Pharmaceutical University (2021-2023)
Osaka University of Pharmaceutical Sciences (2020)

Principal Investigator

Okuhira Keiichiro  大阪医科薬科大学, 薬学部, 教授 (10425671)

Co-Investigator(Kenkyū-buntansha) 清水 太郎  徳島大学, 大学院医歯薬学研究部(薬学域), 特任助教 (30749388)
田中 将史  神戸薬科大学, 薬学部, 教授 (40411904)
石田 竜弘  徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (50325271)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords動脈硬化 / 高密度リポタンパク質 / 高密度リポ蛋白質 / アポリポタンパク質 / アポリポタンタンパク質
Outline of Research at the Start

心筋梗塞や脳卒中といった動脈硬化性疾患において、一般的に「悪玉」と呼ばれるLDL(低密度リポタンパク質)に対して「善玉」HDL(高密度リポタンパク質)は、予防的、抑制的に働くと言われています。本研究では、このHDLの質を高める結合因子の研究を進めて、新しい動脈硬化治療薬の実現を目指しています。

Outline of Final Research Achievements

High-density lipoprotein (HDL) is known to show preventive effects against atherosclerotic diseases such as myocardial infarction and ischemic stroke by releasing lipids from lesions and suppressing inflammation. In this study, we demonstrated that the inflammatory effect of ApoA-I binding protein (AIBP) and the distribution of AIBP expression in vivo, and showed that AIBP could be used for the prevention and treatment against atherosclerosis.

Academic Significance and Societal Importance of the Research Achievements

HDLが動脈硬化に対して予防的・抑制的に働くことは知られているが、HDLを利用することによって動脈硬化を治療する薬はまだ実現していない。本研究によって得られた研究成果の学術的・社会的意義は、HDLの作用を増強すると考えられるAIBPの機能が明らかとなり、AIBPタンパク質が動脈硬化に対する予防や治療に利用されうることが示されたという点にある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Massachusetts General Hospital(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Massachusetts General Hospital(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Massachusetts General Hospital(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Massachusetts General Hospital(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages2022

    • Author(s)
      Tachibana Koki、Kusumoto Kohshi、Ogawa Mai、Ando Hidenori、Shimizu Taro、Ishima Yu、Ishida Tatsuhiro、Okuhira Keiichiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 23 Pages: 14617-14617

    • DOI

      10.3390/ijms232314617

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Effects of Sulforaphane and Allyl Isothiocyanate on 3T3-L1 Adipogenesis2022

    • Author(s)
      Sakuma Satoru、Yasuda Kana、Kitahara Risa、Tsujimoto Kaho、Yamashita Kishiko、Hoshino Naohiro、Fujimoto Yohko、Okuhira Keiichiro
    • Journal Title

      Journal of Nutrition and Metabolism

      Volume: 2022 Pages: 1-8

    • DOI

      10.1155/2022/8705163

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors.2021

    • Author(s)
      Kinoshita R, Ishima Y, Chuang VTG, Watanabe H, Shimizu T, Ando H, Okuhira K, Otagiri M, Ishida T, Maruyama T
    • Journal Title

      Pharmaceutics.

      Volume: 13 Issue: 8 Pages: 1209-1209

    • DOI

      10.3390/pharmaceutics13081209

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice2021

    • Author(s)
      Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
    • Journal Title

      ACS Applied Bio Materials

      Volume: 268 Issue: 5 Pages: 4302-4309

    • DOI

      10.1021/acsabm.1c00110

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Effects of Luteolin and Quercetin on Adipogenesis in 3T3-L1 Cells2021

    • Author(s)
      Sakuma Satoru、Yabuuchi Midori、Yoshizumi Ayumi、Okajima Yui、Fujimoto Yohko、Okuhira Keiichiro
    • Journal Title

      Journal of Pharmacy and Nutrition Sciences

      Volume: 11 Pages: 65-72

    • DOI

      10.29169/1927-5951.2021.11.09

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequence-Independent Traceless Method for Preparation of Peptide/Protein Thioesters Using CPaseY-Mediated Hydrazinolysis2020

    • Author(s)
      Ueda Masahiro、Komiya Chiaki、Arii Sayuki、Kusumoto Kohshi、Denda Masaya、Okuhira Keiichiro、Shigenaga Akira、Otaka Akira
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 68 Issue: 12 Pages: 1226-1232

    • DOI

      10.1248/cpb.c20-00674

    • NAID

      130007948412

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2020-12-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apolipoprotein A‐I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high‐density lipoproteins assembled by ABCA1 and LCAT2020

    • Author(s)
      Tsujita Maki、Vaisman Boris、Chengyu Liu、Vickers Kasey C.、Okuhira Kei‐ichiro、Braesch‐Andersen Sten、Remaley Alan T.
    • Journal Title

      FEBS Letters

      Volume: 595 Issue: 6 Pages: 773-788

    • DOI

      10.1002/1873-3468.13950

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment2019

    • Author(s)
      Ishima Yu、Mimono Ai、Tuan Giam Chuang Victor、Fukuda Tetsuya、Kusumoto Kohshi、Okuhira Keiichiro、Suwa Yoshiaki、Watanabe Hiroshi、Ishida Tatsuhiro、Morioka Hiroshi、Maruyama Toru、Otagiri Masaki
    • Journal Title

      IUBMB Life

      Volume: 72 Issue: 4 Pages: 641-651

    • DOI

      10.1002/iub.2203

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ApoA-1結合タンパク質(AIBP)によるHDLの抗炎症効果への影響2023

    • Author(s)
      永尾 綾菜、樹山 友絵、三輪 保翔、立花 洸季、楠本 嵩志、羽渕 康容、佐久間 覚、奥平 桂一郎
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The magnetic field treated wild-type mice, and in untreated Abca1-null mice reduced the adult-neurogenesis at the hippocampal dentate gyrus2022

    • Author(s)
      Maki Tsujita, Hiroshi Takase, Keito Furuie, Motonari Tsubaki, Keiichiro Okuhira, Frank J Gonzalez, Natsuko Kumamoto, Shinya Ugawa
    • Organizer
      ABC2023 - 9th FEBS Special Meeting ATP-Binding Cassette (ABC) Proteins: From Multidrug Resistance to Genetic Diseases
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ApoA-1 binding protein の加齢に伴う血清中濃度の変化およびその抗炎症作用2022

    • Author(s)
      立花洸季, 楠本嵩志, 前橋梨花, 樹山友絵, 永尾綾菜, 辻田麻紀, 異島優, 石田竜弘, 奥平桂一郎
    • Organizer
      フォーラム2022 衛生薬学・環境トキシコロジー
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗炎症タンパク質ApoA-1 binding protein の加齢に伴う血清中濃度の変化2022

    • Author(s)
      立花洸季, 楠本嵩志, 前橋梨花, 樹山友絵, 永尾綾菜, 辻田麻紀, 異島優, 石田竜弘, 奥平桂一郎
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] SulforaphaneはPRDM16経路を介して白色脂肪細胞のベージュ化を誘導する2022

    • Author(s)
      服部菜々美, 佐久間覚, 奥平桂一郎
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 3T3-L1細胞を用いた白色脂肪細胞のベージュ化関連遺伝子発現に対するスルフォラファンの影響2022

    • Author(s)
      東南 百花、佐久間 覚、奥平 桂一郎
    • Organizer
      日本薬学会第141年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 免疫抑制剤フィンゴリモドによるABCトランスポーターの増加を介した泡沫化マクロファージへの脂質蓄積への影響2021

    • Author(s)
      立花 洸季、小川 真依、石田 竜弘、異島 優、奥平 桂一郎
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 多発性硬化症治療薬FTY720によるABCトランスポーターA1発現に対する影響とそのメカニズム2021

    • Author(s)
      小川 真依、立花 洸季、石田 竜弘、奥平 桂一郎
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] SAA and conditional SR-BI null mice plasma2021

    • Author(s)
      Maki Tsujita, Juniki Yamamoto, Rinka Maehashi, Alan T Remaley, Chieko Mineo, Philip W Shaul, Shinji Yokoyama and Keiichiro Okuhira
    • Organizer
      19th International Symposium on Atherosclerosis (ISA2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 磁場照射によるABCA1トランスポーター機能とマウス成体脳細胞新生への影響2021

    • Author(s)
      辻田麻紀、高瀬博嗣、奥平桂一郎、鍔木基成
    • Organizer
      第1回トランスポーター研究会関西部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 免疫抑制剤フィンゴリモドがマクロファージへの脂質蓄積に与える影響2021

    • Author(s)
      立花 洸季、小川 真依、石田 竜弘、異島 優、奥平 桂一郎
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 3T3-L1前駆脂肪細胞の分化誘導に対するスルフォラファン及びアリルイソチオシアネートの影響2021

    • Author(s)
      佐久間 覚、奥平 桂一郎
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脂質トランスポーターABCA7の発現制御機構解明に向けた研究2020

    • Author(s)
      奥平 桂一郎
    • Organizer
      第15回トランスポーター研究会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 動脈硬化性疾患を標的としたHDL創薬への挑戦2020

    • Author(s)
      奥平 桂一郎
    • Organizer
      徳島大学大学院医歯薬学研究部・BRIGHT合同公開シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 大阪医科薬科大学 衛生化学研究室

    • URL

      https://www.oups.ac.jp/academics/lab/hgn.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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