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イオン排泄・再吸収メカニズムの膜蛋白細胞内局在機構からの解明

Research Project

Project/Area Number 15689005
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionTohoku University

Principal Investigator

種本 雅之  東北大学, 病院, 助手 (40303945)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000)
Fiscal Year 2005: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2004: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2003: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
Keywordsイオンチャネル / 腎臓 / 尿細管 / 高血圧 / 細胞内蛋白局在 / イオンホメオスターシス / 再吸収機構 / プロテオーム / トランスポーター / 細胞内局在 / ホメオスターシス
Research Abstract

本年度の研究では、腎臓イオン排泄・再吸収メカニズムの調節因子として、体液ホメオスターシスや血圧コントロールにおける重要な因子であり、前年度までの研究でその構成因子を解明していた遠位尿細管基底膜側カリウムチャネルの細胞内での機能局在機構の解明を更に進めた。
チャネルの基底膜側への発現が構成因子であるKir4.1サブユニットのカルボキシル末端部の2つの特異的モチーフ配列(di-hydophobic motifとPDZ-binding motif)により規定されることを解明した(J Am Soc Nephrol 16:2608-14,2005)。この結果、di-hydophobic motifが細胞表面への機能発現を制御し、PDZ-binding motifが基底膜側への局在を制御することを解明した。更にyeast two hybrid法を用い腎cDNAライブラリーをスクリーニングすることにより、Kir4.1のカルボキシル末端部と特異的に相互作用する蛋白断片の単離に成功している。断片の配列を用いることにより、機能局在を制御に関連するモチーフ配列を認識しカリウムチャネルの局在を制御する蛋白の同定を進めており、その解明により腎尿細管におけるイオン排泄・再吸収メカニズムに関与するプロテオミクスの解明を進行中である。プロテオミクスの解明に基づき体液ホメオスターシスや高血圧に関する新たな治療法の解明へ発展させる予定である。
また、高血圧疾患に対する臨床治療の立場から、二次性高血圧の主因の一つである腎血管性高血圧の早期診断法の指標を明らかにし(Hypertens Res 28:237-242,2005)、その新たな治療法の提示を行った(J Vasc Surg 41:898-901,2005)。

Report

(3 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 Other

All Journal Article (22 results) Patent(Industrial Property Rights) (1 results) Publications (6 results)

  • [Journal Article] PDZ-binding and di-hydrophobic motifs regulate distribution of Kir4.1 channels in renal cells.2005

    • Author(s)
      Tanemoto M, Abe T, Ito S.
    • Journal Title

      J Am Soc Nephrol 16

      Pages: 2608-2614

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cutting balloon angioplasty of resistant renal artery stenosis caused by fibromuscular dysplasia.2005

    • Author(s)
      Tanemoto M, Abe T, Chaki T, Ishibashi T, Satoh F, Ito S.
    • Journal Title

      J Vasc Surg 41

      Pages: 898-901

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bilateral calcified renal artery aneurysms in a patient with von Recklinghausen's disease.2005

    • Author(s)
      Tanemoto_M, Abe T, Satoh F, Ito S.
    • Journal Title

      Nephrol Dial Transpl 20

      Pages: 1007-1008

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reply.2005

    • Author(s)
      Tanemoto M, Ito S.
    • Journal Title

      J Vasc Surg 42

      Pages: 1039-1040

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Renal Artery Dissection after Angiographic Evaluation of Lower Extremities.2005

    • Author(s)
      Tanemoto M, Abe M, Satoh F, Abe T, Ito S.
    • Journal Title

      Hypertens Res 28

      Pages: 853-855

    • NAID

      10018367321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasma renin activity revealed renal artery stenosis concealed by aneurysms.2005

    • Author(s)
      Tanemoto M, Abe T, Satoh F, Ito S.
    • Journal Title

      Urology 65

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Predictors of Undiagnosed Renal Artery Stenosis among Japanese Patients with Risk Factors of Atherosclerosis.2005

    • Author(s)
      Tanemoto M, Saitoh H, Satoh F, Satoh H, Abe T, Ito S.
    • Journal Title

      Hypertens Res 28

      Pages: 237-242

    • NAID

      40006752036

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 循環血漿量を制御する分子機構の解明.2005

    • Author(s)
      種本雅之, 茶木辰治, 佐藤文俊, 阿部高明, 伊藤貞嘉.
    • Journal Title

      血圧 13

      Pages: 271-274

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 内分泌細胞機能維持に係わる分子の制御法へのアプローチ2005

    • Author(s)
      種本雅之, 茶木辰治, 佐藤文俊, 阿部高明, 伊藤貞嘉.
    • Journal Title

      日本内分泌学会雑誌 81

      Pages: 87-87

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 拡張困難な腎動脈狭窄に対するcutting balloonの効果とその適応2005

    • Author(s)
      種本雅之, 茶木辰治, 阿部倫明, 佐藤文俊, 阿部高明, 石橋忠司, 竹内和久, 伊藤貞嘉.
    • Journal Title

      日本腎臓学会誌 47

      Pages: 342-342

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Predictors of Undiagnosed Renal Artery Stenosis among Japanese Patients with Risk Factors of Atherosclerosis.2005

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      Hypertens Res (印刷中)

    • NAID

      40006752036

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cutting balloon angioplasty of resistant renal artery stenosis caused by fibromuscular dysplasia.2005

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      J Vasc Surg (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bilateral calcified renal artery aneurysms in a patient with von Recklinghausen's disease.2005

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      Nephrol Dial Transpl (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Plasma renin activity revealed renal artery stenosis concealed by aneurysms.2005

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      Urology (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The organic anion transporter (OATP) family.2004

    • Author(s)
      Mikkaichi T et al.
    • Journal Title

      Drug Metab Pharmacokinet 171-9

      Pages: 171-179

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney.2004

    • Author(s)
      Mikkaichi T et al.
    • Journal Title

      Proc Natl Acad Sci U S A 101

      Pages: 3569-3574

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PDZ binding motif dependent localization of K+ channel on basolateral-side in distal tubules.2004

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      Am J Physiol Renal Physiol 287

    • Related Report
      2004 Annual Research Report
  • [Journal Article] レニン-アンギオテンシン系阻害薬の併用療法が有効であった重症高血圧3症例2004

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      Japanese J Nephrol 46

      Pages: 277-277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 酸・塩基平衡調節カリウムチャネルKir5.1/Kir4.1のヒト腎臓における発現分布2004

    • Author(s)
      Tanemoto M et al.
    • Journal Title

      日本内分泌学会雑誌 80

      Pages: 198-198

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 動脈硬化性腎動脈動脈狭窄症の危険因子-Magnetic Resonance Angiography (MRA)による検討2004

    • Author(s)
      Saitoh H et al.
    • Journal Title

      Japanese J Nephrol 46

      Pages: 277-277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 原発性アルドステロン症の局在診断2004

    • Author(s)
      Satoh F et al.
    • Journal Title

      日本内分泌学会雑誌 80

      Pages: 112-112

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 褐色細胞腫診断における生化学的検査の評価について2004

    • Author(s)
      Suzuki S et al.
    • Journal Title

      日本内分泌学会雑誌 80

      Pages: 203-203

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 血圧制御に関与する新たなタンパク質による血圧制御因子のスクリーニング2005

    • Inventor(s)
      種本 雅之, 伊藤 貞嘉, 阿部 高明
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Number
      2005-371148
    • Filing Date
      2005-12-23
    • Related Report
      2005 Annual Research Report
  • [Publications] Mikkaichi T et al.: "Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney."Proc Natl Acad Sci U S A. 101. 3569-3574 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanemoto M et al.: "Successful treatment of severe hypertension with combination of angiotensin converting enzyme inhibitor and angiotensin II receptor blocker."Hypertens Res.. 26. 863-868 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Adachi H et al.: "Molecular characterization of human and rat organic anion transporter OATP-D."Am J Physiol Renal Physiol.. 285. F1188-F1197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki T et al.: "Identification and characterization of novel rat and human gonad specific organic anion transporters."Mol Endocrinol.. 17. 1203-1215 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato K et al.: "Expression of Organic Anion Transporting Polypeptide E(OATP-E) in Human Placenta."Placenta.. 24. 144-148 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanemoto M.et al.: "カリウムチャネルKir5.1/Kir4.1 heteromerによる酸・塩基平衡の調節"Japanese J Nephrol. 45. 225 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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