西村 友宏 (ニシムラ トモヒロ)

Nishimura, Tomohiro

写真a

所属(所属キャンパス)

薬学部 薬学科 薬剤学講座 (芝共立)

職名

准教授

経歴 【 表示 / 非表示

  • 2007年04月
    -
    2008年03月

    共立薬科大学, 助手

  • 2008年04月
    -
    2013年03月

    慶應義塾大学, 薬学部, 助教

  • 2011年09月
    -
    2012年08月

    マウントサイナイ医科大学, 訪問科学者

  • 2014年04月
    -
    2017年03月

    慶應義塾大学, 薬学部, 専任講師

  • 2017年04月
    -
    継続中

    慶應義塾大学, 薬学部, 准教授

学歴 【 表示 / 非表示

  • 2007年03月

    金沢大学

    大学院, 修了, 博士後期

学位 【 表示 / 非表示

  • 博士(薬学), 金沢大学, 課程, 2007年03月

免許・資格 【 表示 / 非表示

  • 甲種危険物取扱者, 2000年12月

  • 薬剤師, 2004年04月

 
 

著書 【 表示 / 非表示

  • 今日のOTC薬.

    中島恵美., 南江堂, 東京, 2009年04月

    担当範囲: 1-624

  • 今日のOTC薬.

    Emi Nakashima, Akihiko Ito., 南江堂, 東京, 2009年03月

    担当範囲: 374-379

  • トランスポーター科学最前線. 血液胎盤関門トランスポーターの機能.

    中島恵美, 崔吉道, 西村友宏., 京都/京都廣川書店, 2008年02月

    担当範囲: 135-154

論文 【 表示 / 非表示

  • Quantification of ENT1 and ENT2 Proteins at the Placental Barrier and Contribution of These Transporters to Ribavirin Uptake

    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 of Pharmaceutical Sciences (Journal of Pharmaceutical Sciences)  108 ( 12 ) 3917 - 3922 2019年12月

    ISSN  00223549

     概要を見る

    © 2019 The Authors The aims of this study are to quantify the protein levels of nucleoside transporters in placental microvillous membranes (MVMs) and to clarify the contributions of these transporters to ribavirin uptake at the placental barrier. Placental MVMs of human and rat expressed equilibrative nucleoside transporter (ENT) 1 protein, whereas the expression of ENT2 protein was obscure. Maternal-to-fetal transfer of [3H]ribavirin in rats was much higher than that of [14C]sucrose. The uptake of [3H]ribavirin by rat placental trophoblast TR-TBT 18 d-1 cells, which functionally express both ENT1 and ENT2 proteins, was saturable, and was significantly inhibited by 0.1 μM nitrobenzylthioinosine, which selectively abolishes ENT1-mediated uptake. Dipyridamole at 10 μM is capable of inhibiting ENT2 as well as ENT1, but a degree of inhibition by 10 μM dipyridamole on [3H]ribavirin uptake was not much different from that by 0.1 μM nitrobenzylthioinosine (ENT1-specific inhibitor). Therefore, ENT2 may contribute little to [3H]ribavirin uptake by these cells. Rat ENT1 cRNA-injected oocytes showed increased [3H]ribavirin uptake compared with water-injected oocytes, while rat ENT2 cRNA-injected oocytes did not. In conclusion, ENT1 protein expressed in placental MVMs appears to play a predominant role in the uptake of ribavirin.

  • LAT1-Targeting Thermoresponsive Liposomes for Effective Cellular Uptake by Cancer Cells

    Maekawa-Matsuura M., Fujieda K., Maekawa Y., Nishimura T., Nagase K., Kanazawa H.

    ACS Omega (ACS Omega)  4 ( 4 ) 6443 - 6451 2019年04月

     概要を見る

    © 2019 American Chemical Society. L-type amino acid transporter 1 (LAT1) is a transporter that is more highly expressed in cancer cells compared with normal cells. In the present study, liposomes, composed of egg phosphatidylcholine (EPC) and dioleoyl phosphatidylethanolamine, were modified with LAT1-targeting thermoresponsive polymer, l-tyrosine-conjugated poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)). The cellular uptake of the prepared LAT1-targeting liposomes was evaluated using HeLa cells as a cancer cell model. At temperatures above the polymer's lower critical solution temperature, uptake of the liposomes into cells was observed because the polymer at the liposome surface became hydrophobic and interacted with the cell membrane. Flow cytometry analysis suggested that l-tyrosine-P(NIPAAm-co-DMAAm)-liposomes exhibited markedly increased cellular uptake by HeLa cells compared with that of liposomes not modified with l-tyrosine. This result indicated that cellular uptake of liposomes can be enhanced by the affinity between l-tyrosine and the LAT1 of HeLa cells. The developed functional liposomes, which exhibit both thermoresponsive and LAT1-targeting properties, would be appropriate for temperature-modulated drug delivery and imaging with good targeting ability.

  • Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line

    Takahashi Y., Nishimura T., Higuchi K., Noguchi S., Tega Y., Kurosawa T., Deguchi Y., Tomi M.

    Pharmaceutical Research (Pharmaceutical Research)  35 ( 12 )  2018年12月

    ISSN  07248741

     概要を見る

    © 2018, The Author(s). Purpose: The anti-epileptic drug pregabalin crosses the blood-brain barrier (BBB) in spite of its low lipophilicity. This study was performed to determine whether L-type amino acid transporters (LAT1/SLC7A5 and LAT2/SLC7A8) contribute to the uptake of pregabalin. Methods: Pregabalin uptake by LATs-transfected HEK293 cells or hCMEC/D3 cells, an in vitro human BBB model, was measured by LC-MS/MS analysis. Expression of LAT1 mRNA in hCMEC/D3 cells was determined by quantitative RT-PCR analysis. Results: Overexpression of LAT1, but not LAT2, in HEK293 cells significantly increased the cellular uptake of pregabalin, and the LAT1-mediated uptake was saturable with a Km of 0.288 mM. LAT1-mediated amino acid uptake was inhibited specifically and almost completely in the presence of 1 mM pregabalin. The uptake of pregabalin by hCMEC/D3 cells was sodium-independent, saturable (Km = 0.854 mM), and strongly inhibited by large amino acids at 1 mM, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, a specific system L inhibitor, at 1 mM and by JPH203, a LAT1-selective inhibitor, at 10 μM. Pregabalin uptake in hCMEC/D3 cells was also decreased by 75% by the silencing of LAT1 gene using LAT1 siRNA. Conclusions: Our results indicate that LAT1, but not LAT2, recognizes pregabalin as a substrate. It is suggested that LAT1 mediates pregabalin transport at the BBB.

  • LAT1-targeting thermoresponsive fluorescent polymer probes for cancer cell imaging

    Matsuura M., Ohshima M., Hiruta Y., Nishimura T., Nagase K., Kanazawa H.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  19 ( 6 )  2018年06月

    ISSN  16616596

     概要を見る

    © 2018 by the authors. Licensee MDPI, Basel, Switzerland. L-type amino acid transporter 1 (LAT1) is more highly expressed in cancer cells compared with normal cells. LAT1 targeting probes would therefore be a promising tool for cancer cell imaging. In this study, LAT1-targeting thermoresponsive fluorescent polymer probes based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) were synthesized and their affinity for LAT1 was evaluated. The synthesized polymer probes interacted with LAT1 on HeLa cells, and inhibition of L-[3 H]-leucine, one of the substrates for LAT1 uptake, was investigated. L-Tyrosine-conjugated P(NIPAAm-co-DMAAm) inhibited the uptake of L-[3 H]-leucine, while P(NIPAAm-co-DMAAm) and L-phenylalanine-conjugated P(NIPAAm-co-DMAAm) did not. This result indicated that L-tyrosine-conjugated polymer has a high affinity for LAT1. The fluorescent polymer probes were prepared by modification of a terminal polymer group with fluorescein-5-maleimide (FL). Above the polymer transition temperature, cellular uptake of the polymer probes was observed because the polymers became hydrophobic, which enhanced the interaction with the cell membrane. Furthermore, quantitative analysis of the fluorescent probe using flow cytometry indicated that L-tyrosine-conjugated P(NIPAAm-co-DMAAm)-FL shows higher fluorescence intensity earlier than P(NIPAAm-co-DMAAm)-FL. The result suggested that cellular uptake was promoted by the LAT1 affinity site. The developed LAT1-targeting thermoresponsive fluorescent polymer probes are expected to be useful for cancer cell imaging.

  • Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6

    Nishimura T., Higuchi K., Yoshida Y., Sugita-Fujisawa Y., Kojima K., Sugimoto M., Santo M., Tomi M., Nakashima E.

    Biological and Pharmaceutical Bulletin (Biological and Pharmaceutical Bulletin)  41 ( 10 ) 1523 - 1529 2018年

    ISSN  09186158

     概要を見る

    © 2018 The Pharmaceutical Society of Japan. Hypotaurine is a precursor of taurine and a physiological antioxidant that circulates in adult and fetal plasma. The purpose of the present study was to clarify whether hypotaurine is a substrate of Slc6a/gammaaminobutyric acid (GABA) transporter family members. Radiolabeled hypotaurine was synthesized from radiolabeled cysteamine and 2-aminoethanethiol dioxygenase. The uptakes of [3H]GABA, [3H]taurine, and [14C]hypotaurine by HEK293 cells expressing mouse GAT1/Slc6a1, TAUT/Slc6a6, GAT3/Slc6a11, BGT1/ Slc6a12, and GAT2/Slc6a13 were measured. TAUT and GAT2 showed strong [14C]hypotaurine uptake activity, while BGT1 showed moderate activity, and GAT1 and GAT3 showed slight but significant activity. Mouse TAUT and GAT2 both showed Michaelis constants of 11 μM for hypotaurine uptake. GAT2-expressing cells pretreated with hypotaurine showed resistance to H2O2-induced oxidative stress. These results suggest that under physiological conditions, TAUT and GAT2 would be major contributors to hypotaurine transfer across the plasma membrane, and that uptake of hypotaurine via GAT2 contributes to the cellular resistance to oxidative stress.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • Mother-to-fetus transfer of antiviral drugs and the involvement of transporters at the placental barrier.

    Tomi M, Nishimura T, Nakashima E*.

    J Pharm Sci (WILEY-BLACKWELL)  100(9)   3708-3718 2011年09月

    総説・解説(学術雑誌), 共著

研究発表 【 表示 / 非表示

  • 胎盤を介した胎児からのクレアチニン排出輸送機構の解析

    山下稔貴、西村友宏、中島恵美 、登美斉俊

    日本薬学会第137年会 (仙台) , 2017年03月

  • Hypotaurineおよびその供給因子の胎盤組織内分布

    斉藤慶、西村友宏、中島恵美 、登美斉俊

    日本薬学会第137年会 (仙台) , 2017年03月

  • SLC6Aファミリーによるヒポタウリン輸送と酸化ストレスに対する細胞保護作用

    西村友宏、 樋口慧、中島恵美、登美斉俊

    第38回生体膜と薬物の相互作用シンポジウム (名古屋) , 2016年11月

  • げっ歯類合胞体栄養膜細胞層におけるMDR1およびBCRPの局在

    登美斉俊、明石知也、高木良也、中島恵美、西村友宏

    第24回日本胎盤学会学術集会 (和歌山) , 2016年11月

  • マウス胎盤内プロスタグランジンPGE2 分解に果たす輸送体の役割

    稲垣舞、西村友宏、中西猛夫、島田 紘明、赤沼伸乙、立川正憲、細谷健一、玉井郁巳、中島恵美、登美斉俊

    日本薬物動態学会第31年会 松本 (松本) , 2016年10月

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競争的資金等の研究課題 【 表示 / 非表示

  • 降圧薬同効薬間の有害事象報告頻度比較分析に基づく妊娠高血圧症治療薬開拓

    2018年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 西村 友宏, 基盤研究(C), 補助金,  代表

  • サリドマイド類の精液移行と胎児への影響

    2016年04月
    -
    2017年03月

    日本医療研究開発機構(AMED), 医薬品等規制調和・評価研究事業, 西村友宏, 代表

  • 胎盤における母体環境ストレス緩和初動因子の機能発現制御

    2015年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 西村 友宏, 基盤研究(C), 補助金,  代表

  • エズリンを基軸とする胎児発育制御分子ネットワーク

    2014年04月
    -
    2015年03月

    上原記念生命科学財団

  • エズリンをシードジーンとする胎盤機能制御遺伝子ネットワーク解析

    2013年04月
    -
    2015年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 西村 友宏, 若手研究(B), 補助金,  代表

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受賞 【 表示 / 非表示

  • 崔 吉道, 樋口 慧, 和田真実, 巨勢典子, 西村友宏, 田村 淳, 月田早智子, 若山友彦, 中島恵美., 2007年06月, トランスポーター研究会, ラット胎盤におけるezrinの発現変動とP-glycoproteinおよびGLUT1細胞内局在への影響.

    受賞区分: 国内学会・会議・シンポジウム等の賞

 

担当授業科目 【 表示 / 非表示

  • 薬物動態学1

    2019年度, 兼任

  • 薬物動態学2

    2019年度, 兼任

  • アプライド薬物動態学

    2019年度, 春学期, 専任

  • 薬品機能解析・動態制御学特論

    2019年度

  • 卒業研究(薬科学科)

    2019年度

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