Studies for cellular and whole-body boric-acid homeostasis in human and mouse

• Project/Area Number: 25650114
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Animal physiology/Animal behavior
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KATO Akira 東京工業大学, 生命理工学研究科, 助教 (40311336)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA Toru 東京大学, 農学生命科学研究科, 教授 (80242163)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ホウ酸 / ホメオスタシス / Slc4a11 / アクアポリン / イオン輸送体 / 細胞増殖

Outline of Final Research Achievements

In vertebrates, boric acid is a vital micronutrient that is required for embryogenesis and cell growth. High [boric acid] is toxic to animals, however, little is known about the whole-body boric acid homeostasis. We found that marine teleosts, e.g., Takifugu obscurus and Takifugu rubripes, excrete and concentrate boric acid in the urine to eliminate excess boric acid, and identified channels for borate (Slc4a11) and boric acid (AQP3, 7, 8, 9a, 9b) in pufferfish. To clarify the presence of similar systems in mammals, the functions of mammalian Slc4a11 and AQPs were analyzed using ion-selective microelectrodes. Human AQP3, 7, 8, 9, 10 showed boric acid and water channel activities. However, human and mouse Slc4a11 showed no significant borate-transport activity. These results indicate that mammalian boric acid homeostasis is mainly maintained by AQP family whereas that of marine teleosts is regulated by Slc4a11 and AQPs.

Academic Significance and Societal Importance of the Research Achievements

ホウ素は植物の細胞壁を構成する元素の１つとして知られ、その重要性や代謝について植物を用いた研究が進んでいる。一方、動物でもホウ素は微量栄養素とされているが、その機能や代謝を担う分子メカニズムは明らかでない。本研究により、哺乳動物や魚類の細胞の細胞膜に存在するホウ酸輸送体を特定した。その結果、腸でホウ酸を吸収する経路や腎臓でホウ酸を排出する経路についてさらに詳細に解析することが可能になり、哺乳動物がホウ酸を代謝する経路の理解に大きく貢献することが期待される。

Research Products

• [Journal Article] Na+/H+ and Na+/NH4+ activities of zebrafish NHE3b expressed in Xenopus oocytes. (2014)
  • Author(s): Ito Y, Kato A, Hirata T, Hirose S, Romero MF
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 306(5) Issue: 5 Pages: R315-R327
  • DOI: 10.1152/ajpregu.00363.2013
  • Peer Reviewed
• [Presentation] アフリカツメガエル卵母細胞を用いたNa+/NH4+交換輸送体の活性測定 (2014)
  • Author(s): 加藤明，平田拓，伊藤雄介，広瀬茂久，Michael F. Romero
  • Organizer: 第9回トランスポーター研究会年会
  • Place of Presentation: 名古屋市立大学、名古屋
  • Year and Date: 2014-06-14 – 2014-06-15
• [Presentation] Pufferfish Slc4a11 functions as a borate channel for borate secretion (2013)
  • Author(s): Kato A, Kimura Y, Kurita Y, Chang MH, Kasai K, Fujiwara T, Hirata T, Doi H, Hirose S, Romero MF
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, USA
• [Presentation] メフグの淡水・海水適応を担うイオン輸送体の解析 (2013)
  • Author(s): 加藤 明
  • Organizer: 東京大学大気海洋研究所共同利用研究集会
  • Place of Presentation: 柏
  • Invited
• [Presentation] Transporters maintaining the delicate balance between necessity and toxicity of boric acid/borate (2013)
  • Author(s): Kato A, Kimura Y, Hayashi N, Kurita Y, Chang MH, Kasai K, Fujiwara T, Hirata T, Islam Z, Doi H, Romero MF, Hirose S
  • Organizer: Biomedical Transporters 2013
  • Place of Presentation: St. Moritz, Switzerland
  • Invited
• [Presentation] 排出型ホウ酸イオンチャネルの同定 (2013)
  • Author(s): 加藤 明，木村 友梨，栗田 志広，Min-Hwang Chang，笠井 光治，藤原 徹，平田 拓，土井 啓行，Michael F. Romero，広瀬 茂久
  • Organizer: 第17回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪