Detection of BSEP mediated hepatotoxicity by using the intrahepatic bile acid imaging technique

• Project/Area Number: 21790141
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Chiba University
• Principal Investigator: SEKINE Shuichi Chiba University, 大学院・薬学研究院, 助教 (70401007)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 薬学 / 薬剤反応性 / 蛋白質 / 放射線 / 薬剤反応生

Research Abstract

Among 25 hepatotoxic compounds, we could newly detect 9 compounds which caused BSEP internalization. And also, we could confirm the increase of hepatotoxicity caused by the BSEP internalization-induced accumulation of bile acid in sandwiched rat hapatocytes.

Research Products

• [Journal Article] LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats. (2011)
  • Author(s): Saeki J, Sekine S, Yano K, Hashimoto N, Horie T.
  • Journal Title: Biochem Pharmacol. 81(1) Pages: 178-184
  • Peer Reviewed
• [Journal Article] LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats. (2011)
  • Author(s): Saeki J, Sekine S, Yano K, Hashimoto N, Horie T.
  • Journal Title: Biochem Pharmacol. Volume: 81 Pages: 178-184
  • Peer Reviewed
• [Journal Article] Oxidative stress is a triggering factor for LPS-induced Mrp2 internalization in the cryopreserved rat and human liver slices. (2010)
  • Author(s): Sekine S, Yano K, Saeki J, Hashimoto N, Fuwa T, Horie T.
  • Journal Title: Biochem Biophys Res Commun. 399(2) Pages: 279-285
  • Peer Reviewed
• [Journal Article] The effect of dimerumic acid on LPS-induced downregulation of Mrp2 in the rat. (2010)
  • Author(s): Yoan K, Sekine S, Nemoto K, Fuwa T, Horie T.
  • Journal Title: Biochem Pharmacol. 80(4) Pages: 533-539
  • Peer Reviewed
• [Journal Article] Zonula Occludens-1 alterations and enhanced intestinal permeability in methotrexate-treated rats. (2010)
  • Author(s): Hamada K, Shiara Y, Sekine S, Horie T.
  • Journal Title: Cancer Chemother Pharmacol. 66(6) Pages: 1031-1038
  • Peer Reviewed
• [Journal Article] Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats. (2010)
  • Author(s): Maeda T, Miyazono Y, Ito K, Hamada K, Sekine S, Horie T.
  • Journal Title: Cancer Chemother Pharmacol. 65(6) Pages: 1117-1123
  • Peer Reviewed
• [Journal Article] Oxidative stress is a triggering factor for LPS-induced Mrp2 internalization in the cryopreserved rat and human liver slices. (2010)
  • Author(s): Sekine S, Yano K, Saeki J, Hashimoto N, Fuwa T, Horie T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 399 Pages: 279-285
  • Peer Reviewed
• [Journal Article] The effect of dimerumic acid on LPS-induced downregulation of Mrp2 in the rat. (2010)
  • Author(s): Yano K, Sekine S, Nemoto K, Fuwa T, Horie T.
  • Journal Title: Biochem Pharmacol. Volume: 80 Pages: 533-539
  • Peer Reviewed
• [Journal Article] Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats (2010)
  • Author(s): Maeda, T., Miyazono, Y., Ito.K., Hamada, K., Sekine, S., Horie, T.
  • Journal Title: Cancer.Chemother.Pharmacol. 65 Pages: 1117-1123
  • Peer Reviewed
• [Journal Article] Zonula Occludens-1 alterations and enhanced intestinal permeability in methotrexate-treated rats (2010)
  • Author(s): Hamada, K., Shitara, Y., Sekine, S., Horie, T.
  • Journal Title: Cancer.Chemother.Pharmacol. (印刷中)
  • Peer Reviewed
• [Journal Article] The effect of dimerumic acid on LPS-induced downregulation of Mrp 2 in the rat (2010)
  • Author(s): Yano, K., Sekine, S., Nemoto, K., Fuwa, Toru., Horie, T.
  • Journal Title: Biochemical Pharmacology (印刷中)
  • Peer Reviewed
• [Journal Article] Correlation between apical localization of Abcc2/Mrp2 and phosphorylation status of ezrin in rat intestine. (2009)
  • Author(s): Nakano T, Sekine S, Ito K, Horie T.
  • Journal Title: Drug Metab Dispos. 37(7) Pages: 1521-1527
  • Peer Reviewed
• [Journal Article] Posttranslational regulation of Abcc2 expression by SUMOylation system (2009)
  • Author(s): Minami, S., Ito, K., Honma, M., Ikebuchi, Y., Anzai, N., Kanai, Y., Nishida, T., Tsukita, S., Sekine, S., Horie, T., Suzuki, H.
  • Journal Title: Am.J.Physiol.Gastrointest.Liver.Physiol. 296 Pages: 406-413
  • Peer Reviewed
• [Journal Article] Correlation between apical localization of Abcc2/Mrp2 and phosphorylation status of ezrin in rat intestine (2009)
  • Author(s): Nakano, T., Sekine, S., Ito, K., Horie, T.
  • Journal Title: Drug.Metab.Dispos. 37 Pages: 1521-1527
  • Peer Reviewed
• [Journal Article] Posttranslational regulation of Abcc2 expression by SUMO ylation system. (2008)
  • Author(s): Minami S, Ito K, Honma M, Ikebuchi Y, Anzai N, Kanai Y, Nishida T, Tsukita S, Sekine S, Horie T, Suzuki H.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 296(2)
  • Peer Reviewed
• [Presentation] 肝炎時の胆汁排泄輸送体Mrp2の内在化機構の解明 (2011)
  • Author(s): 佐伯淳二郎、関根秀一、堀江利治
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: 静岡
• [Presentation] C型肝炎ウイルスコア蛋白質により誘発されるミトコンドリア障害に対する徹蓄積の関与 (2011)
  • Author(s): 伊藤好美、関根秀一、堀江利治、小池和彦、森屋恭爾、新谷良澄、藤江肇、堤武也、三好秀征、藤永秀剛、新澤靖子
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: 静岡
• [Presentation] C型肝炎ウイルスコア蛋白質により誘発される酸化ストレスに対する鉄蓄積の関与 (2010)
  • Author(s): 伊藤好美、関根秀一、堀江利治、小池和彦、森屋恭爾、新谷良澄、藤江肇、堤武也、三好秀征、藤永秀剛、新澤靖子
  • Organizer: 第18回 生体パーオキサイド研究会
  • Place of Presentation: 仙台
  • Year and Date: 2010-08-21
• [Presentation] 細胞内レドックス状態の変化によるMrp2-radixin複合体の局在制御機構の解明 (2010)
  • Author(s): 関根秀一、伊藤晃成、堀江利治
  • Organizer: 日本薬剤学会 第25年会
  • Place of Presentation: 徳島
• [Presentation] 小腸におけるMrp2,Mdr1発現部位差とezrinの発現、リン酸化状態の部位差との関連 (2010)
  • Author(s): 関根秀一、中埜貴文、伊藤晁成、堀江利治
  • Organizer: 日本薬剤学会 第25年会
  • Place of Presentation: 徳島
• [Presentation] Regulatory mechanism of drug-induced Bsep internalization by construction of screening system for Bsep internalization (2010)
  • Author(s): Eiichiro Ogimura, Shuichi Sekine, Toshiharu Horie
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮
• [Presentation] The role of Nrf2 on multidrug resistance (2010)
  • Author(s): Masahiro Ono, Shuichi Sekine, Toshiharu Horie
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮
• [Presentation] Canalicular Mrp2 localization is reversibly regulated by the phosphorylation status of its anchoring protein (2010)
  • Author(s): Shuichi Sekine, Kousei Ito, Toshiharu Horie
  • Organizer: 9^<th> International ISSX meeting
  • Place of Presentation: イスタンブール
• [Presentation] Ezrin has a key role in the expression profile of MRP2 and MDR1 along intestinal tract (2010)
  • Author(s): Shuichi Sekine, Kousei Ito, Takafumi, Nakano, Toshiharu Horie
  • Organizer: 9^<th> International ISSX meeting
  • Place of Presentation: イスタンブール
• [Presentation] 薬剤性ミトコンドリア障害感受性における動物種差の検討 (2010)
  • Author(s): 本山碧、関根秀一、木村友映、堀江利治
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山
• [Presentation] 細胞内レドックス状態の変化によるMrp2-radixin複合体の局在制御機構の解明 (2010)
  • Author(s): 関根秀一、伊藤晃成、堀江利治
  • Organizer: 日本薬剤学会 第25年会
  • Place of Presentation: あわぎんホール徳島県郷土文化会館
• [Presentation] 小腸におけるMrp2,Mdr1発現部位差とezrinの発現、リン酸化状態の部位差との関連 (2010)
  • Author(s): 関根秀一、中埜貴文、伊藤晃成、堀江利治
  • Organizer: 日本薬剤学会 第25年会
  • Place of Presentation: あわぎんホール徳島県郷土文化会館
• [Presentation] Regulatory mechanism of drug-induced Bsep internalization by construction of screening system for Bsep internalization (2010)
  • Author(s): Eiichiro Ogimura, Shuichi Sekine, Toshiharu Horie
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックホール
• [Presentation] LPS-induced Mrp2 internalization is due to the dissociation of Mrp2 and radixin (2010)
  • Author(s): Junjiro Saeki, Shuichi Sekine, Toshiharu Horie
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックホール
• [Presentation] The role of Nrf2 on multidrug resistance (2010)
  • Author(s): Masahiro Ono, Shuichi Sekine, Toshiharu Horie
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックホール
• [Presentation] 薬物誘発性ミトコンドリア膜透過性遷移における種差の解明 (2010)
  • Author(s): 関根秀一、設楽悦久、関根秀一
  • Organizer: 第37回 日本トキシコロジー学会学術年会
  • Place of Presentation: 沖縄コンベンションセンター
• [Presentation] Canalicular Mrp2 localization is reversibly regulated by the phosphorylation status of its anchoring protein (2010)
  • Author(s): Shuichi Sekine, Kousei Ito, Toshiharu Horie
  • Organizer: 9^<th> International ISSX meeting
  • Place of Presentation: Istanbul, Tukery
• [Presentation] Ezrin has a key role in the expression profile of MRP2 and MDR1 along intestinal tract (2010)
  • Author(s): Shuichi Sekine, Kousei Ito, Takafumi, Nakano, Toshiharu Horie
  • Organizer: 9^<th> International ISSX meeting
  • Place of Presentation: Istanbul, Tukery
• [Presentation] 薬剤性ミトコンドリア障害感受性における動物種差の検討 (2010)
  • Author(s): 本山碧、関根秀一、木村友映、堀江利治
  • Organizer: 第32回 生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山国際会議場
• [Presentation] 小腸炎症時における薬剤排泄トラシスポーターMrp2の機能制御機構の解明 (2010)
  • Author(s): 小島亮人, 関根秀一, 中埜貴文, 堀江利治
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 肝臓及び小腸における Estradiol 17β-glucuronide誘発性Mrp2機能低下機構の解明 (2010)
  • Author(s): 松尾玲子, 関根秀一, 堀江利治
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] LPS誘発性胆針うっ滞時のMrp2機能低下に対するジメルミン酸の抑制効果について (2010)
  • Author(s): 矢野健太郎, 関根秀一, 根本華奈子, 不破亨, 堀江利治
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] メトトレキサートによる小腸上皮バリア機能障害の機序解析 (2010)
  • Author(s): 濱田和真, 設楽悦久, 関根秀一, 堀江利治
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] Intracellular redox status reversibly regulates the localization of Mrp2-radixin complex. (2009)
  • Author(s): Sekine, Shuichi., Ito, Kousei., Horie, Toshiharu.
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪
• [Presentation] メトトレキサートによる小腸上皮透過性亢進の機序検討 (2009)
  • Author(s): 濱田和真, 設楽悦久, 関根秀一, 堀江利治
  • Organizer: 日本薬剤学会第24年会講演要旨集
  • Place of Presentation: 静岡県コンベンションアーツセンター(グランシップ)
• [Presentation] Oxidative stress contributes to Methotrexate-induced small intestinal in jury caused by neutrophil infiltration (2009)
  • Author(s): Asada, C., Sekine, S., Miyazono, Y., Maeda, T., Horie, T
  • Organizer: The 1st International Conference on Lipid Hydroperoxide Byology and Medicine Sendai(ICLH 2009)
  • Place of Presentation: 仙台
• [Presentation] LPS誘発性胆汁うっ滞における Dimerumic acid の抑制効果について (2009)
  • Author(s): 矢野健太郎, 関根秀一, 根本華奈子, 不破亨, 堀江利治
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 小腸におけるMrp2発現部位差とezrinリン酸化状態との関連 (2009)
  • Author(s): 中埜貴文, 関根秀一, 伊藤晃成, 堀江利治
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 国立京都国際会館
• [Presentation] LPS誘発性Mrp2局在変化へのRadixinの脱リン酸化の関与 (2009)
  • Author(s): 佐伯淳二郎, 関根秀一, 月田早智子, 堀江利治
  • Organizer: 日本薬物動態学会第24回年会学
  • Place of Presentation: 国立京都国際会館
• [Presentation] Intracellular redox status reversibly regulates the localization of Mrp2-radixin complex (2009)
  • Author(s): 関根秀一, 伊藤晃成, 堀江利治
  • Organizer: 第31 回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪
• [Remarks] ホームページ等
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• [Remarks]
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