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Significance of a balanced tryptophan diet for supporting fetal growth

Research Project

Project/Area Number 18H03183
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 InstitutionKeio University

Principal Investigator

Tomi Masatoshi  慶應義塾大学, 薬学部(芝共立), 教授 (30334717)

Co-Investigator(Kenkyū-buntansha) 野口 幸希  慶應義塾大学, 薬学部(芝共立), 助教 (10803661)
伊藤 直樹  帝京大学, 医学部, 講師 (20529177)
牟田 真理子  帝京平成大学, 健康メディカル学部, 教授 (40445193)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordsアミノ酸トランスポーター / 胎盤関門 / カチオントランスポーター
Outline of Final Research Achievements

The purpose of the present study was to clarify the transporters mediating the fetal transfer of tryptophan and examine the importance of an adequate supply of tryptophan into the fetus. This study described the amount and localization of LAT1 protein, a transporter for large neutral amino acids including tryptophan, at the placental barrier. It is also observed that the tissue distribution of LAT1 substrate is suppressed by an increase of LAT1-substrate amino acids in the plasma. For serotonin, we have clarified OCTN1 protein accepts it as a substrate and is expressed at the placental barrier at term. However, the effect of tryptophan imbalance in the diet was negligible in the plasma concentration of amino acids.

Academic Significance and Societal Importance of the Research Achievements

胎児へのトリプトファン(Trp)輸送だけでなく、セロトニン輸送に関与するトランスポーターを解明したことは、胎児環境決定因子を同定できたという点で学術的意義は大きい。また、血中におけるLAT基質アミノ酸の総量に対する一つの基質の存在比率が、当該基質のLAT支配臓器への移行に影響することは示された一方、食事中Trp存在比率の変化が血中アミノ酸組成に与える影響は小さいことが示された。アミノ酸サプリメントには特定のアミノ酸のみを摂取するものもあり、LAT基質アミノ酸の過剰摂取が胎児へのTrp供給に与える影響が限定的であることを総合的に示した本研究は、社会的に重要な意味を持つと考えられる。

Report

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

    (21 results)

All 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] MicroRNA-126 suppresses the invasion of trophoblast-model JEG-3 cells by targeting LIN28A2021

    • Author(s)
      Pan Xiaole、Noguchi Saki、Ando Misuzu、Nishimura Tomohiro、Tomi Masatoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 545 Pages: 132-137

    • DOI

      10.1016/j.bbrc.2021.01.077

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorouracil uptake in triple‐negative breast cancer cells: Negligible contribution of equilibrative nucleoside transporters 1 and 22021

    • Author(s)
      Noguchi Saki、Takagi Akinori、Tanaka Takahiro、Takahashi Yu、Pan Xiaole、Kibayashi Yuka、Mizokami Ryo、Nishimura Tomohiro、Tomi Masatoshi
    • Journal Title

      Biopharmaceutics & Drug Disposition

      Volume: 42 Issue: 2-3 Pages: 85-93

    • DOI

      10.1002/bdd.2261

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of Prostaglandin Transporter OATP2A1/SLCO2A1 to Placenta-to-Maternal Hormone Signaling and Labor Induction2020

    • Author(s)
      Inagaki Mai、Nishimura Tomohiro、Nakanishi Takeo、Shimada Hiroaki、Noguchi Saki、Akanuma Shin-ichi、Tachikawa Masanori、Hosoya Ken-ichi、Tamai Ikumi、Nakashima Emi、Tomi Masatoshi
    • Journal Title

      iScience

      Volume: 23 Issue: 5 Pages: 101098-101098

    • DOI

      10.1016/j.isci.2020.101098

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of ENT1 and ENT2 Proteins at the Placental Barrier and Contribution of These Transporters to Ribavirin Uptake.2019

    • Author(s)
      Nishimura T, Sano Y, Takahashi Y, Noguchi S, Uchida Y, Takagi A, Tanaka T, Katakura S, Nakashima E, Tachikawa M, Maruyama T, Terasaki T, Tomi M.
    • Journal Title

      J Pharm Sci.

      Volume: 108(12) Issue: 12 Pages: 3917-3922

    • DOI

      10.1016/j.xphs.2019.09.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line2018

    • Author(s)
      Takahashi Y, Nishimura T, Higuchi K, Noguchi S, Tega Y, Kurosawa T, Deguchi Y, Tomi M
    • Journal Title

      Pharm Res.

      Volume: 35 Issue: 12 Pages: 246-246

    • DOI

      10.1007/s11095-018-2532-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] プレガバリンのラット脳移行における血漿中LAT1基質アミノ酸の影響2020

    • Author(s)
      野口 幸希, 高橋 優, 西村 友宏, 登美 斉俊
    • Organizer
      第15回トランスポーター研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 薬物の胎盤透過を規定するメカニズムとその影響2020

    • Author(s)
      登美 斉俊, 野口 幸希, 西村 友宏
    • Organizer
      第60回日本先天異常学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 関門としての胎盤:薬物透過制御機構とその種差2020

    • Author(s)
      登美 斉俊, 野口 幸希, 西村 友宏
    • Organizer
      第47回日本毒性学会学術年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウス栄養膜幹細胞3次元培養系における関門機能分子の発現誘導2019

    • Author(s)
      木林由佳、野口幸希、田辺美那子、齋藤義正、西村友宏、登美斉俊
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 血漿タンパク結合率が薬物胎児移行性の種差に及ぼす影響2019

    • Author(s)
      野村岳広、野口幸希、西村友宏、登美斉俊
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] miR-126が栄養膜モデルJEG-3細胞における合胞体化促進因子の発現に与える影響2019

    • Author(s)
      潘曉楽、野口幸希、安藤美鈴、竹村千尋、西村友宏、登美斉俊
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス栄養膜幹細胞3次元培養系における関門機能分子の発現誘導2019

    • Author(s)
      木林由佳、野口幸希、田辺美那子、齋藤義正、西村友宏、登美斉俊
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Possibilities and limitations of extrapolating fetal drug transfer data from rodents to human pregnancy2019

    • Author(s)
      Tomi Masatoshi、Noguchi Saki、Nishimura Tomohiro
    • Organizer
      Asian Federation for Pharmaceutical Sciences (AFPS) 2019 Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] OAT4を介したlosartan carboxylic acidおよびcandesartanのCl-依存性輸送2019

    • Author(s)
      飛田萌子、野口幸希、木村りか、福本文香、西村友宏、登美斉俊
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス栄養膜幹細胞の分化に伴うOATP2A1発現変動とHIF1αの影響2019

    • Author(s)
      井坂真実、西村友宏、稲垣舞、田辺美那子、 野口幸希、登美斉俊
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胎児/母体血漿中非結合形濃度比を用いたdigoxinのラット胎盤透過性評価2019

    • Author(s)
      野村岳広、西村友宏、野口幸希、登美斉俊
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト栄養膜由来JEG-3細胞の分化過程におけるmiR-126の役割2019

    • Author(s)
      潘曉楽、野口幸希、安藤美鈴、竹村千尋、西村友宏、登美斉俊
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] LAT1 が血液脳関門におけるpregabalin 輸送に果たす役割2018

    • Author(s)
      髙橋優、西村友宏、樋口慧、野口幸希、手賀悠真、黒澤俊樹、 出口芳春、登美斉俊
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血液脳関門における中性アミノ酸トランスポーターLAT1 を介したpregabalin輸送2018

    • Author(s)
      "高橋優、西村友宏、樋口慧、野口幸希、手賀悠真、黒澤俊樹、 出口芳春、登美斉俊"
    • Organizer
      第40回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Induction mechanism of MDR1 in mouse trophoblast stem cell differentiation2018

    • Author(s)
      Tanabe M, Noguchi S, Nishimura T, Tomi M
    • Organizer
      International Federation of Placenta Associations (IFPA) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The physiological and pharmacological roles of organic anion transporter 4 in the placenta2018

    • Author(s)
      Tomi M
    • Organizer
      International Federation of Placenta Associations (IFPA) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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

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