Aquaporins involved with diabetes insipidus and the investigation of natural compounds controling the function of aquaporns

• Project/Area Number: 26460223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Usui Shigeyuki 岐阜薬科大学, 薬学部, 准教授 (40176665)
• Co-Investigator(Kenkyū-buntansha): 大山 雅義 岐阜薬科大学, 薬学部, 教授 (30381718)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アクアポリン / 細胞膜移行 / 細胞質移行 / プロテインキナーゼＣ / アクチン / 微小管 / Akt / トラフィキング / AQP1 / AQP3 / AQP9 / オイゲノール / レスベラトロール / ヒト前立腺がん細胞 / プロテインキナーゼC / 緑色蛍光タンパク質 / Ａｋｔ

Outline of Final Research Achievements

Aquaporins which are intrinsic membrane proteins functioning as a water channel permeable to water and glycerol. All aquaporin molecules expressing in cells do not always exist in a cell membrane, but the trafficking of aquaporins in a cell are controlled to move between the cell membrane and inside the cell as necessary. We found that the movement of aquaporin 3 from inside to membrane was regulated by protein kinase C and that from membrane to inside was done by protein kinase B (Akt). Phosphorylation of Thr237 and Ser275 in aquaporin 3 was confirmed to be necessary to move from inside the cell to cell membrane.
We investigated natural compounds which triggered the trafficking of aquaporins. Eugenol which is a component of magnolia flower derived from Magnolia salicifolia was found to promote the trafficking of aquaporin 3 from inside to membrane accompanying the phosphorylation of protein kinase C.

Research Products

• [Journal Article] Anti-Androgenic Activity of Icarisid II from Epimedium Herb in Prostate Cancer LNCaP Cells. (2015)
  • Author(s): oko Miura, Masayoshi Oyama, Kazuhiro Iguchi, Tetsuro Ito, Misako Baba, Yuji Shikama, Shigeyuki Usui, kazuyuki Hirano, Munekazu Iinuma, Hiroshige Mikamo.
  • Journal Title: J Nutr Sci Vitaminol Volume: 62 Pages: 201-204
  • NAID: 130005074115
  • Peer Reviewed
• [Journal Article] Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells. (2014)
  • Author(s): Kazuhiro Iguchi, Maki Hashimoto, Masafumi Kubota, Shuji Yamashita, Mitsuhiro Nakamura, Shigeyuki Usui, Tadashi Sugiyama, and Kazuyuki Hirano
  • Journal Title: Oncol. Lett. Volume: 7 Pages: 1665-1668
  • Peer Reviewed
• [Journal Article] Anti-androgenic activity of hydroxyxanthones in prostate cancer LNCaP cells. (2014)
  • Author(s): Toshinobu Shakui, Kazuhiro Iguchi, Tetsuro Ito, Misako Baba, Shigeyuki Usui, Masayoshi Oyama, Hideki Tosa, Munekazu Iinuma, and Kazuyuki Hirano
  • Journal Title: Fitoterapia Volume: 92 Pages: 9-15
  • Peer Reviewed
• [Presentation] 生薬エキス添加によるアクアポリン3の細胞内局在の変化に関する研究 (2016)
  • Author(s): 四元 珠湖, 曽田 翠, 北市 清幸, 大山 雅義, 臼井 茂之
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-03-29
• [Remarks] なし