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

2010 Fiscal Year Final Research Report

• 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
• Keywords: 薬学 / 薬剤反応性 / 蛋白質 / 放射線

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] 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] 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 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) Pages: G406-G413
  • 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
  • Year and Date: 20110328-20110331
• [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
  • Year and Date: 20110328-20110331
• [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
  • Year and Date: 20101129-20101130
• [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
  • Year and Date: 20101116-20101118
• [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
  • Year and Date: 20101116-20101118
• [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
  • Year and Date: 20100904-20100908
• [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
  • Year and Date: 20100904-20100908
• [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
  • Year and Date: 20100512-20100514
• [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
  • Year and Date: 20100512-20100514
• [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
  • Year and Date: 20091130-20091201
• [Remarks] ホームページ等
  • URL: http://www.p.chiba-u.ac.jp/lab/yakuzai/index.html