Role of oxidative stress-responsive miRNA on the variation of expression and function of protein regulating pharmacokinetics

• Project/Area Number: 23790206
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Mie University (2013); Kinjo Gakuin University (2011-2012)
• Principal Investigator: IKEMURA Kenji 三重大学, 医学部附属病院, 助教 (70513935)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マイクロRNA / P-糖タンパク質 / 薬物体内動態 / 小腸上皮細胞 / 転写後調節 / P－糖蛋白質 / 肝虚血再灌流障害 / 酸化ストレス / 薬物代謝酵素 / タイトジャンクション / P-糖蛋白質 / P-glycoprotein

Research Abstract

We found that microRNA-145 (miR-145) regulates the expression and function of P-glycoprotein (P-gp) in the small intestine. This result provide new insight into the post-transcriptional regulation of intestinal P-gp. Moreover, miRNAs regulate the expression and function of proteins regulating pharmacokinetics in intestinal epithelial cells. Therefore, miRNAs could be significant factors affecting inter- and intra-individual variations in the pharmacokinetics and intestinal absorption of drugs.

Research Products

• [Journal Article] MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions (2014)
  • Author(s): Ikemura K, Iwamoto T, Okuda M
  • Journal Title: Implication for intestinal barrier function. Pharmacol Ther
  • Peer Reviewed
• [Journal Article] MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions: Implication for intestinal barrier function (2014)
  • Author(s): Ikemura K, Iwamoto T, Okuda M
  • Journal Title: Pharmacol Ther Volume: 143 Issue: 2 Pages: 217-224
  • DOI: 10.1016/j.pharmthera.2014.03.002
  • Peer Reviewed
• [Journal Article] Altered pharmacokinetics of cimetidine caused by down-regulation of renal rat organic cation transporter 2 (rOCT2) after liver ischemia-reperfusion injury (2013)
  • Author(s): Ikemura K, Nakagawa E,Kurata T, Iwamoto T, Okuda M
  • Journal Title: Drug Metab Pharmacokinet Volume: 28(6) Pages: 504-509
  • NAID: 130004463334
  • Peer Reviewed
• [Journal Article] MicroRNA-145 post-transcriptionally regulates the expression and function of P-glycoprotein in intestinal epithelial cells (2013)
  • Author(s): Ikemura K, Yamamoto M, Miyazaki S, Mizutani H, Iwamoto T, Okuda M
  • Journal Title: Mol Pharmacol Volume: 83(2) Pages: 399-405
  • Peer Reviewed
• [Journal Article] Altered Pharmacokinetics of Cimetidine Caused by Down-regulation of Renal Rat Organic Cation Transporter 2 (rOCT2) after Liver Ischemia-Reperfusion Injury (2013)
  • Author(s): Ikemura K, Nakagawa E, Kurata T, Iwamoto T, Okuda M
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 6 Pages: 504-509
  • DOI: 10.2133/dmpk.DMPK-13-RG-021
  • NAID: 130004463334
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] MicroRNA-145 post-transcriptionally regulates the expression and function of P-glycoprotein in intestinal epithelial cells. (2013)
  • Author(s): Ikemura et al.
  • Journal Title: Mol Pharmacol. Volume: 83 Issue: 2 Pages: 399-405
  • DOI: 10.1124/mol.112.081844
  • Peer Reviewed
• [Journal Article] An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine (2012)
  • Author(s): Ikemura K, Inoue K, Mizutani H, Oka H, Iwamoto T, Okuda M
  • Journal Title: Eur J Pharmacol Volume: 690(1-3) Pages: 192-201
  • Peer Reviewed
• [Journal Article] An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine. (2012)
  • Author(s): Ikemura K, Inoue K, Mizutani H, Oka H, Iwamoto T, Okuda M.
  • Journal Title: European Journal of Pharmacology Volume: 690(1-3) Pages: 192-201
  • Peer Reviewed
• [Presentation] リスペリドンの急性中毒によりQT延長から心停止に至った１症例 (2014)
  • Author(s): 榎屋友幸, 岩下義明, 池村健治, 中川裕司, 村木優一、岩本卓也, 奥田真弘、武田太一、今井寛
  • Organizer: 第34回日本中毒学会西日本地方会
  • Place of Presentation: 関西医科大学付属枚方病院
• [Presentation] miR-145による小腸上皮細胞P-糖蛋白質の転写後発現調節機構 (2013)
  • Author(s): 池村健治
  • Organizer: 第59回日本薬学会東海支部総会大会
  • Place of Presentation: 名城大学(愛知県名古屋市)
  • Year and Date: 2013-07-06
• [Presentation] miR-145による小腸上皮細胞P-糖蛋白質の転写後発現調節機構 (2013)
  • Author(s): 池村健治, 山本弥里, 宮崎さおり, 水谷秀樹, 岩本卓也, 奥田真弘
  • Organizer: 第59回日本薬学会東海支部総会大会
  • Place of Presentation: 名城大学薬学部
• [Presentation] miR-145は小腸上皮細胞P-糖蛋白質の発現・機能調節に関与する (2012)
  • Author(s): 池村健治
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
• [Presentation] miR-145は小腸上皮細胞P-糖蛋白質の発現・機能調節に関与する (2012)
  • Author(s): 池村健治、山本弥里、宮崎さおり、水谷秀樹、岩本卓也、奥田真弘
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 抗がん性抗生物質イダルビシンによる酸化的 DNA 損傷機構 (2012)
  • Author(s): 水谷秀樹、志賀千秋、池村健治、平工雄介、川西正祐
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学
• [Presentation] Decreased oral absorption of cyclosporine A through elevated intestinal CYP3A and P-glycoprotein by oxidative stress after liver ischemia-reperfusion (2011)
  • Author(s): Kenji Ikemura
  • Organizer: 第5回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 名古屋大学医学部附属病院(愛知県名古屋市)
• [Presentation] 肝虚血再灌流障害時のCyclosporine Aの経口bioavailability低下における酸化ストレスの役割 (2011)
  • Author(s): 池村健治
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: タワーホテル船堀(東京都江戸川区)
• [Presentation] 抗がん性抗生物質アクラルビシンによる酸化的DNA損傷機 (2011)
  • Author(s): 水谷秀樹, 林由佳, 西本彩乃, 池村健治, 平工雄介, 及川(多田)佐枝子, 及川伸二, 村田真理子, 川西正祐
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会 2011
  • Place of Presentation: ウインク愛知
• [Presentation] Decreased oral absorption of cyclosporine A through elevated intestinal CYP3A and P-glycoprotein by oxidative stress after liver ischemia-reperfusion (2011)
  • Author(s): Kenji Ikemura, Hideki Mizutani, Takuya Iwamoto, Masahiro Okuda
  • Organizer: 第5回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 名古屋大学医学部附属病院
• [Presentation] 抗腫瘍性抗生物質マイトマイシンＣによる活性酸素を介したアポトーシス誘導機構 (2011)
  • Author(s): 水谷秀樹、山口可奈、伊藤美穂、渡邉愛子、池村健治、平工雄介、及川（多田）佐枝子、及川伸二、村田真理子、川西正祐
  • Organizer: 第57回日本薬学会東海支部総会大会
  • Place of Presentation: 金城学院大学
• [Presentation] 腫瘍性抗生物質ピラルビシンによる酸化的ＤＮＡ損傷機構 (2011)
  • Author(s): 西本彩乃、水谷秀樹、林由佳、池村健治、平工雄介、及川（多田）佐枝子、及川伸二、村田真理子、川西正祐
  • Organizer: 第57回日本薬学会東海支部総会大会
  • Place of Presentation: 金城学院大学
• [Presentation] ラルテグラビル投与に伴う副作用発現並びに遺伝子多型と血中濃度に関する検討 (2011)
  • Author(s): 山本弥里、平野淳、宮崎さおり、池村健治、高橋昌明、水谷秀樹、柴田雅章、網岡克雄、野村敏治、横幕能行、杉浦亙
  • Organizer: 第５７回日本薬学会東海支部総会大会
  • Place of Presentation: 金城学院大学
• [Presentation] 肝虚血再灌流障害時のCyclosporine Aの経口bioavailability低下における酸化ストレスの役割 (2011)
  • Author(s): 池村健治、井之上浩一、水谷秀樹、岡尚男、村木優一、岩本卓也、奥田真弘
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: タワーホテル船堀
• [Patent(Industrial Property Rights)] マイクロRNA145(miR-145)によるMDR1/P-糖タンパク質(P-gp)の転写後発現調節 (2012)
  • Inventor(s): 池村健治、岩本卓也、奥田真弘
  • Industrial Property Rights Holder: 国立大学法人三重大学,学校法人金城学院
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-096869
  • Filing Date: 2012-04-20