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Development of a novel analysis and evaluation system for environmental chemicals-induced toxicity using toxicolipidomics

Research Project

Project/Area Number 25293033
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionShowa University

Principal Investigator

Hara Shuntaro  昭和大学, 薬学部, 教授 (50222229)

Co-Investigator(Kenkyū-buntansha) KUWATA Hiroshi  昭和大学, 薬学部, 講師 (80286864)
SASAKI Yuka  昭和大学, 薬学部, 助教 (40635108)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords環境化学物質 / リン脂質代謝 / プロスタグランジン / トキシコリピドミクス / 遺伝子改変マウス
Outline of Final Research Achievements

In order to develop a novel analysis and evaluation system for environmental chemicals-induced toxicity, we focused on lipid molecules as targets of toxic chemicals and performed toxicolipidomics, in which we comprehensively investigated alterations in lipid profiles including membrane phospholipid composition and production of bioactive lipids. As the results, we found that treatments of mice with several toxic chemicals such as doxorubicin decreased contents of phospholipids with unsaturated fatty acids and increased peroxidized lipid levels. It was also found that after induction of inflammation or carcinogenesis by chemicals in mouse models, biosyntheses of some bioactive lipids such as prostaglandin E2 were elevated in the lesion sites. We further found that mice genetically modified to alter lipid metabolism were susceptible to some toxic chemicals, indicating that these mice might be useful for highly sensitive evaluation system for chemicals-induced toxicity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (45 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (37 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] Karolinska Institutet(Sweden)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Inhibition of long-chain acyl-coenzyme A synthetase 4 facilitates production of 5,11-dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway2015

    • Author(s)
      Kuwata, H., Hara, S.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 465 Issue: 3 Pages: 525-533

    • DOI

      10.1016/j.bbrc.2015.08.054

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis2015

    • Author(s)
      Sasaki, Y., Hara, S.
    • Journal Title

      Prostaglandins and Other Lipid Mediators

      Volume: 121 Pages: 42-45

    • DOI

      10.1016/j.prostaglandins.2015.06.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1.2015

    • Author(s)
      Sasaki Y, Kamiyama S, Kamiyama A, Matsumoto K, Akatsu M, Nakatani Y, Kuwata H, Ishikawa Y, Ishii T, Yokoyama C, Hara S.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 17376-17376

    • DOI

      10.1038/srep17376

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Secreted phospholipase A2s and mast cells.2015

    • Author(s)
      Murakami, M., and Taketomi, Y.
    • Journal Title

      Allergology Int.

      Volume: 64 Issue: 10 Pages: 4-10

    • DOI

      10.1371/journal.pone.0109409

    • NAID

      130004873126

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein2014

    • Author(s)
      Sasabe N, Keyamura Y, Obama T, Inoue N, Igarashi Y, Aiuchi T, Kato R, Yamaguchi T, Kuwata H, Iwamoto S, Miyazaki A, Hara S, Yoshikawa T, Itabe H
    • Journal Title

      Lipids Health Dis

      Volume: 13 Issue: 1 Pages: 48-48

    • DOI

      10.1186/1476-511x-13-48

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic acid metabolism in interleukin 1β-stimulated rat fibroblasts2014

    • Author(s)
      Kuwata, H., Yoshimura, M., Sasaki, Y., Yoda, E., Nakatani, Y., Kudo, I., Hara, S.
    • Journal Title

      Biochimica et Biophyica Acta - Molecular and Cell Biology of Lipids

      Volume: 1841 Issue: 1 Pages: 44-53

    • DOI

      10.1016/j.bbalip.2013.09.015

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells2013

    • Author(s)
      Ozawa, A., Kadowaki, E., Haga, Y., Sekiguchi, H., Hemmi, N., Kaneko, T., Maki, T., Sakabe, K., Hara, S., Yamamoto, M., Arishima, K., Sakaue, M.
    • Journal Title

      Brain Research

      Volume: 1537 Pages: 37-45

    • DOI

      10.1016/j.brainres.2013.08.031

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] リポ多糖投与により惹起される全身性炎症は長鎖アシルCoA合成酵素4の欠損により増悪化する2016

    • Author(s)
      桑田浩、水沼孝裕、伊藤早紀、原俊太郎
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ca2+非依存性ホスホリパーゼA2(iPLA2)γの大腸化学発がんにおける役割2016

    • Author(s)
      平井玲子、山田亮介、佐々木由香、 依田恵美子、原俊太郎
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] プロスタサイクリン合成酵素(PGIS) の接触性皮膚炎における役割2016

    • Author(s)
      落合翔、佐々木由香、横山知永子、原俊太郎
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 皮膚化学発がんにおけるプロスタグランジン合成酵素の役割2015

    • Author(s)
      佐々木由香、横山知永子、原俊太郎
    • Organizer
      BMB (Biochemistry and Molecular Biology) 2015
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素4の生体内機能解析2015

    • Author(s)
      桑田浩、水沼孝裕、伊藤早紀、原 俊太郎
    • Organizer
      BMB (Biochemistry and Molecular Biology) 2015
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 化学発がんにおけるプロスタグランジン最終合成酵素の役割2015

    • Author(s)
      佐々木由香、原俊太郎
    • Organizer
      フォーラム2015: 衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学ポートアイランドキャンパス(神戸市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素4の生体内機能解析2015

    • Author(s)
      桑田浩、水沼孝裕、伊藤早紀、原 俊太郎
    • Organizer
      フォーラム2015: 衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学ポートアイランドキャンパス(神戸市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 接触性皮膚炎におけるプロスタサイクリン合成酵素(PGIS)の役割2015

    • Author(s)
      落合翔、佐々木由香、横山知永子、原俊太郎
    • Organizer
      第59回日本薬学会関東支部大会
    • Place of Presentation
      日本大学薬学部(船橋市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素4の生体内機能の解析-12015

    • Author(s)
      水沼孝裕、伊藤早紀、森雅美、矢澤将太、桑田浩、原俊太郎
    • Organizer
      第59回日本薬学会関東支部大会
    • Place of Presentation
      日本大学薬学部(船橋市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素4の生体内機能の解析-22015

    • Author(s)
      伊藤早紀、水沼孝裕、矢澤将太、森雅美、桑田浩、原俊太郎
    • Organizer
      第59回日本薬学会関東支部大会
    • Place of Presentation
      日本大学薬学部(船橋市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Microsomal prostaglandin E synthase-1 (mPGES-1) deficiency suppresses chemical carcinogen-induced carcinogenesis2015

    • Author(s)
      Sasaki, Y., Hara, S.
    • Organizer
      14th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
    • Place of Presentation
      Hungarian Academy of Sciences (Budapest, Hungary)
    • Year and Date
      2015-07-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膜結合型プロスタグランジンE合成酵素、mPGES-1の化学発がんへの関与の解析2015

    • Author(s)
      佐々木由香、原俊太郎
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      ホテル日航金沢(金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膜結合型プロスタグランジンE合成酵素(mPGES-1)の発がんにおける役割2015

    • Author(s)
      佐々木由香、会田衣利、原俊太郎
    • Organizer
      第57回日本脂質生化学会
    • Place of Presentation
      一橋大学一橋講堂(東京都千代田区)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 酸化LDL生成時におけるリン脂質プロファイルの経時変化とLp-PLA2の役割2015

    • Author(s)
      笹部直子、毛谷村由佳、小浜孝士、井上望、増子幸志、五十嵐優、相内敏弘、加藤里奈、山口智広、桑田浩、原俊太郎、吉川智博、板部洋之
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸市)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞内ホスホリパーゼA2によるケモカインの発現機構の解析2015

    • Author(s)
      平川裕士、桑田浩、原俊太郎
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸市)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗ガン剤ドキソルビシンを用いた脂質酸化感知モデルマウスによる心毒性の解析2015

    • Author(s)
      幸村知子、一ノ瀬栞、中村仁美、福山達也、清水敦子、池田麻美、桑田浩、原俊太郎、今井浩孝
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸市)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膜結合型プロスタグランジンE合成酵素の皮膚発がんへの関与の解析2015

    • Author(s)
      会田衣利、佐々木由香、蛭田凌平、原俊太郎
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸市)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Involvement of calcium-independent phospholipase A2γ (iPLA2γ) in tumor growth2015

    • Author(s)
      Hara, S., Yoda, E., Nakatani, Y., Nakayama, S., Suzuki, Y., Kondo, Y.
    • Organizer
      6th International Conference on Phospholpase A2 and Lipid Mediators (PLM2015) from bench to translational medicine
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of microsomal prostaglandin E synthase-1 in chemical-induced carcinogenesis2015

    • Author(s)
      Sasaki, Y., Hara, S.
    • Organizer
      6th International Conference on Phospholpase A2 and Lipid Mediators (PLM2015) from bench to translational medicine
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-02-10 – 2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inhibition of acyl-CoA synthetase perturbs arachidonic acid metabolism2015

    • Author(s)
      Kuwata, H., Hara, S.
    • Organizer
      6th International Conference on Phospholpase A2 and Lipid Mediators (PLM2015) from bench to translational medicine
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-02-10 – 2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Involvement of microsomal prostaglandin E synthase-1-derived prostaglandin E2 in chemical-induced carcinogenesis2014

    • Author(s)
      Hara, S., Sasaki, Y.
    • Organizer
      5th European Workshop on Lipid Mediators
    • Place of Presentation
      University of Istanbul (Istanbul, Turkey)
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素の阻害による脂肪酸代謝変動の解析2014

    • Author(s)
      桑田浩、庄司知紘、福島有彩、原俊太郎
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膜結合型Ca2+非依存性ホスホリパーゼA2(iPLA2γ)は癌細胞増殖に関わる2014

    • Author(s)
      堀川亮、依田恵美子、原俊太郎
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 癌細胞背部皮下移植モデルを用いた細胞質型Ca2+非依存性ホスホリパーゼA2(iPLA2β)の機能解析2014

    • Author(s)
      山田亮介、依田恵美子、原俊太郎
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 癌細胞背部皮下移植モデルを用いた膜結合型Ca2+非依存性ホスホリパーゼA2(iPLA2γ)の機能解析2014

    • Author(s)
      森角裕貴、依田恵美子、原俊太郎
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素の阻害による脂肪酸代謝変動の解析2014

    • Author(s)
      桑田浩、島田浩明、庄司知紘、福島有彩、原俊太郎
    • Organizer
      フォーラム2014: 衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Phospholipid metabolism in calcium-independent phospholipase A2γ-deficient platelets2014

    • Author(s)
      Hara, S., Yoda, E., Kuwata, H.
    • Organizer
      55th International Conference on the Bioscience of Lipids (ICBL2014)
    • Place of Presentation
      Robert Gordon University (Aberdeen, Scotland, UK)
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] プロスタグランジン最終合成酵素mPGES-1およびPGISの二重遺伝子欠損マウスの表現型解析2014

    • Author(s)
      原俊太郎、佐々木由香、横山知永子
    • Organizer
      第56回日本脂質生化学会
    • Place of Presentation
      近畿大学東大阪キャンパス(東大阪市)
    • Year and Date
      2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] 長鎖アシルCoA合成酵素の阻害による脂肪酸代謝変動に関する研究2014

    • Author(s)
      桑田浩、島田浩明、福島有彩、原俊太郎
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 全身性膜結合型カルシウム非依存性ホスホリパーゼA2 過剰発現マウスの解析2014

    • Author(s)
      依田恵美子、吉田麗菜、武富芳隆、原俊太郎
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アラキドン酸代謝物産生におけるアシルCoA合成酵素の役割2013

    • Author(s)
      桑田浩、島田浩明、原俊太郎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 全身性膜結合型カルシウム非依存性ホスホリパーゼA2過剰発現マウスは胎児期の発達異常を示す2013

    • Author(s)
      依田恵美子、吉田麗菜、武富芳隆、原俊太郎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] カルシウム非依存性ホスホリパーゼA2によるケモカイン産生機構の解析2013

    • Author(s)
      池上悠貴、木下夏海、鷲尾彩菜、原田和佳、依田恵美子、桑田浩、原俊太郎
    • Organizer
      フォーラム2013: 衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学医学部百年講堂(福岡市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アラキドン酸代謝物産生における長鎖アシルCoA合成酵素の役割2013

    • Author(s)
      桑田浩、島田浩明、福島有彩、鷲巣沙彩、原俊太郎
    • Organizer
      フォーラム2013: 衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学医学部百年講堂(福岡市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アラキドン酸代謝反応における長鎖アシルCoA合成酵素の役割2013

    • Author(s)
      福島有彩、鷲巣沙彩、桑田浩、原俊太郎
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      帝京大学薬学部(東京都板橋区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Effect of gene deletion of two prostaglandin terminal synthases, PGIS and mPGES-1 on adiposity in mice2013

    • Author(s)
      Sasaki, Y., Akatsu, M., Yamakawa, Y., Yokoyama, C., Hara, S.
    • Organizer
      13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
    • Place of Presentation
      Sheraton Puerto Rico (San Juan, Puerto Rico, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genetic deletion of prostacylin synthase, a cyclooxygenase-2 downstream enzyme, in mice promotes carcinogenesis in contrast to that of microsomal prostaglandin E synthase-12013

    • Author(s)
      Hara, S., Sasaki, Y., Yokoyama, C.
    • Organizer
      13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
    • Place of Presentation
      Sheraton Puerto Rico (San Juan, Puerto Rico, USA)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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