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Fetal transfer mechanism of methyl donors across the placenta and its epigeneomes

Research Project

Project/Area Number 25560063
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Eating habits
Research InstitutionKeio University

Principal Investigator

TOMI Masatoshi  慶應義塾大学, 薬学部, 准教授 (30334717)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Tomohiro  慶應義塾大学, 薬学部, 専任講師 (40453518)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胎盤関門 / トランスポーター / メチル基供与体
Outline of Final Research Achievements

We aimed to examine the fetal transfer mechanism of methyl donors, such as methionine, 5-methyltatrahydrofolate (MTHF), and betaine, across the placenta. LAT1, a transporter for methionine, was observed to be specifically localized at the brush-border membrane of rat placental syncytiotrophoblast layer I, suggesting the role of LAT1 in the fetal transfer of amino acids. Fetal transfer rate of 5-methyltatrahydrofolate (MTHF) and betaine appears to be low compared with methionine transported by LAT1, implying the importance of methionine in terms of placental permeability. SNAT2 mediates the transfer of betaine, and its functional expression in placental brush-border membrane was found to be detected in rat but not in human. This suggests the presence of the species difference in betaine transport. Methylated CpG level in the promoter region of the Abcg2 gene was observed to be very low.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Invited: 5 results)

  • [Journal Article] Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts2015

    • Author(s)
      Nishimura T, Duereh M, Sugita Y, Yoshida Y, Higuchi K, Tomi M, Nakashima E.
    • Journal Title

      Placenta

      Volume: 36 Issue: 6 Pages: 693-698

    • DOI

      10.1016/j.placenta.2015.02.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Organic anion transporter 4-mediated transport of olmesartan at basal plasma membrane of human placental barrier2015

    • Author(s)
      Noguchi S, Nishimura T, Fujibayashi A, Maruyama T, Tomi M, Nakashima E.
    • Journal Title

      J Pharm Sci

      Volume: 104 Issue: 9 Pages: 3128-3135

    • DOI

      10.1002/jps.24434

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of protein kinase A in regulating steroid sulfate uptake for estrogen production in human placental choriocarcinoma cells2014

    • Author(s)
      Tomi M, Miyata Y, Noguchi S, Nishimura S, Nishimura T, Nakashima E.
    • Journal Title

      Placenta

      Volume: 35 Issue: 8 Pages: 658-660

    • DOI

      10.1016/j.placenta.2014.06.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] System amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.2014

    • Author(s)
      Nishimura T, Yagi R, Usuda M, Oda K, Yamazaki M, Suda S, Takahashi Y, Okazaki F, Sai Y, Higuchi, K, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      Biochim Biophys Acta.

      Volume: VOL. 1838 Issue: 5 Pages: 1306-12

    • DOI

      10.1016/j.bbamem.2014.01.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト胎盤関門トランスポーターによる胎児防御機構と薬物輸送制御2015

    • Author(s)
      登美斉俊、西村友宏、中島恵美
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Respective contribution system A subtypes to neutral amino acid transport at the placental microvillous membrane2014

    • Author(s)
      Takahashi Y, Nishimura T, Suda S, Tomi M, Nakashima E.
    • Organizer
      19th North American ISSX Meeting and 29th JSSX Annual Meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-10-19 – 2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Uptake mechanism of an estriol precursor, 16α-hydroxy dehydroepiandrosterone sulfate, at the basal plasma membrane of human term placenta2014

    • Author(s)
      Tomi M, Eguchi H, Nishimura T, Maruyama T, Nakashima E.
    • Organizer
      International Federation of Placenta Associations 2014
    • Place of Presentation
      Paris
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬物の胎児移行における胎盤トランスポーターのインパクト2014

    • Author(s)
      登美斉俊、西村友宏、中島恵美
    • Organizer
      第30回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 薬物胎児移行支配要因としての胎盤トランスポーター2014

    • Author(s)
      登美斉俊、西村友宏、中島恵美
    • Organizer
      医療薬学フォーラム2014・第22回クリニカルファーマシーシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-06-28 – 2014-06-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 胎盤刷子縁膜中性アミノ酸輸送におけるSystem Aサブタイプ別寄与率の評価2014

    • Author(s)
      高橋優、西村友宏、須田沙也加、登美斉俊、中島恵美
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬物胎児移行性の支配要因となるヒト胎盤トランスポーターの同定と定量評価2014

    • Author(s)
      登美斉俊
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] SNAT2-specific transport function of betaine among amino acid transport system A subtypes.2013

    • Author(s)
      Eguchi H, Nishimura T, Usuda M, Suda S, Tomi M, Nakashima E.
    • Organizer
      International Federation of Placenta Associations (IFPA) 2013
    • Place of Presentation
      Whistler, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine.2013

    • Author(s)
      Eguchi H, Nishimura T, Usuda M, Suda S, Tomi M, Nakashima E.
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2013
    • Place of Presentation
      Jeju, Republic of Korea
    • Related Report
      2013 Research-status Report
  • [Presentation] The impact of placental transporters in creating the dynamic maternal-fetal interface2013

    • Author(s)
      Tomi M, Nishimura T, Nakashima E.
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2013
    • Place of Presentation
      Jeju, Republic of Korea
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Fetus uptake index (FUI) 法を用いた水溶性生体内物質のラット胎盤関門透過性の評価.2013

    • Author(s)
      登美斉俊、小澤英輝、佐野雄一朗、勝部彬、西村友宏、中島恵美
    • Organizer
      第8回トランスポーター研究会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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