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Physiological role of Na-dependent dicarboxylate transporters in central nervous system

Research Project

Project/Area Number 17K08430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionRitsumeikan University

Principal Investigator

FUJITA Takuya  立命館大学, 薬学部, 教授 (00247785)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsクエン酸輸送 / 中枢神経 / クエン酸トランスポーター / クエン酸回路 / クエン酸回路中間体 / 神経細胞 / 発現調節機構 / 輸送活性調節機構 / クエン酸 / TCA回路中間体 / Na+共役クエン酸トランスポーター / CREB / Na+依存性クエン酸輸送担体 / TCA回路 / 薬理学 / 薬物動態学 / Na依存性ジカルボン酸トランスポーター / mammalian Indy (mIndy)
Outline of Final Research Achievements

Neuronal cells reproduce neurotransmitters in cellular pool by using extracellular TCA cycle intermediates. We demonstrated that TCA cycle intermediates, such as α-ketoglutarate and malate, are synthesized in astrocytes, and then they are transported into neuronal cells mediated by Na+-coupled citrate transporter (NaCT/Slc13a5). Transport activity of NaCT was significantly reduced by stimulation of protein kinase C activator (PMA), and reversed by addition of PKC inhibitor Go6983 in a concentration dependent manner. These results indicate that PKC-mediated regulation of NaCT might be responsible for expression level of NaCT protein in neuronal plasma membrane.

Academic Significance and Societal Importance of the Research Achievements

中枢神経系における神経伝達物資の合成や神経活動に必要なエネルギー供給機構の解明は、認知症やてんかん等の神経疾患発症の原因の解明の一助となると考えられる。また、クエン酸トランスポーターは、現在でも患者の治療ニーズに十分にこたえられていない精神疾患治療薬の新たなターゲット分子となる可能性が示唆された。一方、クエン酸トランスポーターは、糖尿病時に肝細胞においても発現が上昇し、肝臓における脂質合成の促進に関与することや非アルコール性脂肪肝への関与も示されていることから、今後の精神疾患治療薬のみならず生活習慣病治療薬開発に対して有益な情報を提供することができると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017 Other

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Transport Characteristics of 5-Aminosalicylic Acid Derivatives Conjugated with Amino Acids <i>via</i> Human H<sup>+</sup>-Coupled Oligopeptide Transporter PEPT12020

    • Author(s)
      Tatsushi Yuri, Yusuke Kono, Tomofumi Okada, Tomohiro Terada, Seiji Miyauchi, Takuya Fujita
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 4 Pages: 697-706

    • DOI

      10.1248/bpb.b19-01048

    • NAID

      130007825299

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-04-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transport characteristics of 5-aminosalicylic acid into colonic epithelium: Involvement of sodium-coupled monocarboxylate transporter SMCT1-mediated transport system2020

    • Author(s)
      Yuri Tatsushi、Kono Yusuke、Fujita Takuya
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524 Issue: 3 Pages: 561-566

    • DOI

      10.1016/j.bbrc.2020.01.139

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of contribution of BCRP to intestinal absorption of various drugs using portal‐systemic blood concentration difference model in mice2020

    • Author(s)
      Kawahara Iichiro、Nishikawa Satoyo、Yamamoto Akira、Kono Yusuke、Fujita Takuya
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 8 Issue: 1

    • DOI

      10.1002/prp2.544

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Openable Artificial Intestinal Tract System Enables the Evaluation of Drug Absorption in Caco-2 Cells through the Reduction in Thickness of the Unstirred Water Layer2019

    • Author(s)
      Yusuke Kono, Satoshi Konishi and Takuya Fujita
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 5 Pages: 840-844

    • DOI

      10.1248/bpb.b18-00921

    • NAID

      130007641451

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-05-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein Kinase C Regulates the Citrate Transport via Na+-Coupled Citrate Transporter NaCT in HepG2 Cells2019

    • Author(s)
      Maya Goto、Yusuke Kono、Ayako Yuki、Haruka Nishimura、Mizuki Ikawa、Kanta Ohno、Takuya Fujita
    • Journal Title

      BPB Reports

      Volume: 2 Pages: 134-140

    • NAID

      130007940491

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmaceutical stability of colloidal saccharated iron oxide injection in normal saline2018

    • Author(s)
      Daiki Hira, Asami Suzuki, Yusuke Kono, Kosuke Shimokawa, Serika Matsuoka, Ken-yuh Hasumoto, Hiroyuki Kawahara, Masahide Onoue, Takuya Fujita, Tomonobu Okano and Mikio Kakumoto
    • Journal Title

      J. Pharm. Health Care Sci.

      Volume: 4 Issue: 1 Pages: 1-6

    • DOI

      10.1186/s40780-018-0116-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of surface charge, particle size, and modification by polyethylene glycol of liposomes on their association with Caco-2 cells across an unstirred water layer.2018

    • Author(s)
      Yusuke Kono, Ayu Iwasaki and Takuya Fujita
    • Journal Title

      Pharmazie

      Volume: 73 Pages: 3-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells2017

    • Author(s)
      Yusuke Kono, Hitomi Jinzai, Yota Kotera and Takuya Fujita
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 12 Pages: 2166-2174

    • DOI

      10.1248/bpb.b17-00563

    • NAID

      130006235423

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of magnetic anionic liposome/atelocollagen complexes for efficient magnetic drug targeting.2017

    • Author(s)
      Yusuke Kono, Taketo Nakai, Hitomi Taguchi and Takuya Fujita
    • Journal Title

      Drug Delivery

      Volume: 24 Issue: 1 Pages: 1740-1749

    • DOI

      10.1080/10717544.2017.1402219

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 糖尿病発症時における Na+ 依存性クエン酸トランスポーターの発現変動に関する研究2019

    • Author(s)
      原田千裕、後藤真耶、大野寛太、河野裕允、根来亮介、藤田卓也
    • Organizer
      第69回日本薬学会関西支部総会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨格筋細胞 C2C12 における Na+ 非依存性中性アミノ酸トランスポーターの活性調節機構の解明2019

    • Author(s)
      飯田千景、河野裕允、藤田卓也
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] HepG2 細胞における cyclic AMP による Na+-dependent citrate transporter (SLC13A5) の発現上昇機構の解明2019

    • Author(s)
      井川瑞貴、河野裕允、藤田卓也
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] HepG2 細胞における Na+-dependent citrate transporter (SLC13A5) の PKC による輸送活性調節機構2019

    • Author(s)
      後藤真耶、結城綾子、西村春香、河野裕允、藤田卓也
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Transport Characteristics of Amino Acids-Conjugated 5-aminosalicylic Acid Derivatives via H+-Coupled Oligopeptide Transporter 12019

    • Author(s)
      Tatsushi Yuri, Yusuke Kono, Tomohiro Terada, Takuya Fujita
    • Organizer
      2019 AAPS Pharm Sci 360
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 金属イオンによるNa+ 依存性クエン酸トランスポーターの輸送活性調節機構2018

    • Author(s)
      西村春香、結城綾子、後藤真耶、河野裕允、藤田卓也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] HepG2細胞におけるNa+ 依存性クエン酸トランスポーターの活性調節機構2018

    • Author(s)
      結城綾子、西村春香、後藤真耶、河野裕允、藤田卓也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 外部磁場を利用した組織選択的細胞送達に向けた磁性化間葉系幹細胞の作製2018

    • Author(s)
      大庭 健、平岡芹菜、松田浩司、河野裕允、藤田卓也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ドキソルビシン内封磁性負電荷リポソーム/アテロコラーゲン複合体のin vitro殺細胞効果の評価2018

    • Author(s)
      田口ひとみ、河野裕允、藤田卓也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 異なる混合比からなる磁性負電荷リポソーム/アテロコラーゲン複合体の細胞内取り込み効率および免疫応答の評価2018

    • Author(s)
      小寺陽太、河野裕允、藤田卓也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト網膜上皮ARPE-19細胞株におけるエンケファリン輸送活性の制御機構解析2018

    • Author(s)
      松岡芹佳、西村春香、結城綾子、河野裕允、角本幹夫、藤田卓也
    • Organizer
      医療薬学フォーラム2018/第26回クリニカルファーマシーシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] In Vitro Devices for Estimating Intestinal Absorption of New Chemical Entities.2018

    • Author(s)
      Takuya Fujita
    • Organizer
      University British Colombia - Ritsumeikan University MEMS Workshop
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] HepG2細胞でのNa+依存性クエン酸輸送における金属イオンの影響2017

    • Author(s)
      結城綾子、西村春香、後藤真耶、船橋理子、河野裕允、藤田卓也
    • Organizer
      医療薬学フォーラム2017/第25回クリニカルファーマシーシンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経細胞における Na+, Cl- 依存性エンケファリン輸送特性の検討2017

    • Author(s)
      西村春香、松岡芹佳、結城綾子、河野裕允、角本幹夫、藤田卓也
    • Organizer
      医療薬学フォーラム2017/第25回クリニカルファーマシーシンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Pharmacokinetic Study in Drug Delivery Stage.2017

    • Author(s)
      Takuya Fujita
    • Organizer
      University Hawaii - Ritsumeikan University Workshop
    • Related Report
      2017 Research-status Report
    • Invited
  • [Remarks] 立命館大学研究者データベース・藤田卓也

    • URL

      http://research-db.ritsumei.ac.jp/Profiles/40/0003910/profile.html

    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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