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Elucidation of a novel pool mechanism of B vitamins through lysosome accumulation

Research Project

Project/Area Number 18KK0453
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionNagoya City University

Principal Investigator

Yasujima Tomoya  名古屋市立大学, 医薬学総合研究院(薬学), 講師 (50753555)

Project Period (FY) 2018 – 2020
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Keywordsトランスポーター / リソソーム / ピリドキシン / ビタミンプール / lysosome / ビタミン / チアミン
Outline of Final Research Achievements

As a result of detailed functional analysis of the novel transporter lysosomal multivitamin transporter 1 (LMVT1), the pyridoxine transport mediated by LMVT1 was driven by cotransport with protons. It was suggested to play a role in supplying pyridoxine from lysosomes into the cytoplasm, suggesting that it may be involved in the excretion and transport of various vitamins including pyridoxine from lysosome in an acidic environment to cytoplasm in a neutral pH environment. In addition, when the substrate recognition of LMVT1 was investigated, it was found that LMVT1 also transports compounds other than vitamins (drugs and bioactive substances). Taken these finding, LMVT1 may be involved in the regulation of pharmacokinetics and various physiological functions.

Academic Significance and Societal Importance of the Research Achievements

生体において、葉酸(ビタミンB9)の細胞内プール機構の存在は知られていたが、本研究成果は、葉酸以外の水溶性ビタミンにおいても、細胞内にプールされる機構が備わっていることを強く示唆するものである。この知見は、世界で初めて見出されたものであり、学術的意義は非常に高いと考えられる。また、本知見を応用することにより、効果的なビタミン摂取法の提案が可能になると期待され、社会的意義も大きいと考えられる。

Report

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

    (14 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (7 results) Remarks (1 results)

  • [Int'l Joint Research] カリフォルニア大学 アーバイン校(米国)2019

    • Year and Date
      2019-10-22
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Proinflammatory cytokines inhibit thiamin uptake by human and mouse pancreatic acinar cells: involvement of transcriptional mechanism(s)2021

    • Author(s)
      Anandam Kasin Yadunandam、Srinivasan Padmanabhan、Yasujima Tomoya、Al-Juburi Saleh、Said Hamid M.
    • Journal Title

      American Journal of Physiology-Gastrointestinal and Liver Physiology

      Volume: 320 Issue: 1 Pages: G108-G116

    • DOI

      10.1152/ajpgi.00361.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Posttranscriptional regulation of thiamin transporter-1 expression by microRNA-200a-3p in pancreatic acinar cells2020

    • Author(s)
      Ramamoorthy Kalidas、Anandam Kasin Yadunandam、Yasujima Tomoya、Srinivasan Padmanabhan、Said Hamid M.
    • Journal Title

      American Journal of Physiology-Gastrointestinal and Liver Physiology

      Volume: 319 Issue: 3 Pages: G323-G332

    • DOI

      10.1152/ajpgi.00178.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates2020

    • Author(s)
      Yamashiro Takahiro、Yasujima Tomoya、Said Hamid M.、Yuasa Hiroaki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 50 Pages: 16998-17008

    • DOI

      10.1074/jbc.ra120.013610

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the amino acid residue responsible for the myricetin sensitivity of human proton-coupled folate transporter2019

    • Author(s)
      Yamashiro Takahiro、Yasujima Tomoya、Ohta Kinya、Inoue Katsuhisa、Yuasa Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18105-18105

    • DOI

      10.1038/s41598-019-54367-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 18β-glycyrrhetyl-3-O-sulfate would be a causative agent of licorice-induced pseudoaldosteronism2019

    • Author(s)
      Ishiuchi Kan’ichiro、Morinaga Osamu、Ohkita Takeshi、Tian Chuanting、Hirasawa Asuka、Mitamura Miaki、Maki Yasuhito、Kondo Tsubasa、Yasujima Tomoya、Yuasa Hiroaki、Minamizawa Kiyoshi、Namiki Takao、Makino Toshiaki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1587-1587

    • DOI

      10.1038/s41598-018-38182-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] SLC19A3の脳神経変性疾患関連遺伝子変異と輸送機能との関係2020

    • Author(s)
      三宅浩平、小川有沙、山城貴弘、保嶋智也、湯浅博昭
    • Organizer
      薬学会,140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] SLC19A3によるpyridoxine及びthiamineの輸送に対するフラボノイド類の阻害作用の解析2020

    • Author(s)
      山下紗瑛奈、山城貴弘、保嶋智也、湯浅博昭
    • Organizer
      薬学会,140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Functional characterization of the carrier-mediated nicotinamide transport system in HepG2 cells2019

    • Author(s)
      難波莉子、保嶋智也、山城貴弘、湯浅博昭
    • Organizer
      薬物動態学会,34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Species differences in SLC19A3 for pyridoxine transport function2019

    • Author(s)
      三宅浩平、高橋駿介、山城貴弘、保嶋智也、湯浅博昭
    • Organizer
      薬物動態学会,34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Functional identification of SLC19A2/3 as pyridoxine transporters2019

    • Author(s)
      山城貴弘、保嶋智也、湯浅博昭
    • Organizer
      薬物動態学会,34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] SLC19A3に対するフラボノイド類の阻害作用2019

    • Author(s)
      山下紗瑛奈、山城貴弘、保嶋智也、湯浅博昭
    • Organizer
      病院薬剤師会東海ブロック/薬学会東海支部合同学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] PCFTの葉酸輸送機能におけるmyricetin感受性に関与するアミノ酸残基の同定2019

    • Author(s)
      山城貴弘、保嶋智也、太田欣哉、井上勝央、湯浅博昭
    • Organizer
      生体膜と薬物の相互作用シンポジウム,41回
    • Related Report
      2019 Research-status Report
  • [Remarks] 名古屋市立大学 大学院薬学研究科 薬物動態制御学分野

    • URL

      http://www.phar.nagoya-cu.ac.jp/hp/yzg/index.html

    • Related Report
      2019 Research-status Report

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Published: 2019-02-06   Modified: 2022-01-27  

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