Comprehensive analysis of prostasin activators and inhibitors and its application for the elucidation of blood pressure regulation

• Project/Area Number: 19590956
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: KITAMURA Kenichiro Kumamoto University, 医学部・附属病院, 講師 (10304990)
• Co-Investigator(Kenkyū-buntansha): 冨田 公夫 熊本大学, 大学院・医学薬学研究部, 教授 (40114772)
• Co-Investigator(Renkei-kenkyūsha): TOMITA Kimio 熊本大学, 大学院・医学薬学研究部, 教授 (40114772)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 水 / 電解質代謝学 / ナトリウムチャネル / セリンプロテアーゼ / プロスタシン / 高血圧

Research Abstract

私たちは上皮型Naチャネル活性化因子であるセリンプロテアーゼのプロスタシンに対するアクチベーターを同定し、プロテアーゼによる血圧調節機構の分子基盤を解明しようと考えた。ラット腎臓組織からzymography法を用いて、プロスタシンのアクチベーター活性を指標に30kDaのタンパク質の分離に成功した。LC-MS/MS法によりカリクレインであることが判明し、現在、カリクレイン-プロスタシンカスケードが上皮型Naチャネル活性に与える影響を検討中である。

Research Products

• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats (2009)
  • Author(s): Kakizoe, Y., Kitamura, K., Wakida, N., Ko, T., Maekawa, A., Miyoshi, T., Shiraishi, N., Adachi, M., Zhang, Z., Masilamani, S. and Kimio Tomita
  • Journal Title: J. Hypertens (in press)
  • Peer Reviewed
• [Journal Article] Urinary prostasin in humans : relationships among prostasin, aldosterone and epithelial sodium channel activity (2009)
  • Author(s): Koda, A., Wakida, N., Toriyama, K., Yamamoto, K., Iijima, H., Tomita, K., and Kitamura, K.
  • Journal Title: Hypertens. Res. 32 Pages: 276-281
  • NAID: 10024830568
  • Peer Reviewed
• [Journal Article] Camostat mesilate inhibits prostasin activity, and reduces blood pressure and renal injury in salt-sensitive hypertension (2009)
  • Author(s): Maekawa, A., Kakizoe, Y., Miyoshi, T., Wakida, N., Ko, T., Shiraishi, N., Adachi, M., Tomita, K., and Kitamura, K.
  • Journal Title: J. Hypertens 27 Pages: 181-189
  • Peer Reviewed
• [Journal Article] Effect of intravenous iron administration frequency on oxidative stress in chronic hemodialysis patients (2008)
  • Author(s): Kitamura, K., Anraku, M., Shintomo, R., Takeuchi, K., Ikeda, H., Nagano, J., Ko, T., Mera, K., Tomita, K., and Otagiri, M.
  • Journal Title: Clin. Biochem. 41 Pages: 1168-1174
  • Peer Reviewed
• [Journal Article] Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans (2008)
  • Author(s): Anzai, N., Ichida, K., Jutabha, P., Kimura, T., Babu, E., Jin, C.J., Srivastava, S., Kitamura, K., Hisatome, I., Endou, H., and Sakurai, H.
  • Journal Title: J. Biol. Chem 283 Pages: 26834-26838
  • Peer Reviewed
• [Journal Article] CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products (2008)
  • Author(s): Iwao, Y., Nakajou, K., Nagai, R., Kitamura, K., Anraku, M., Maruyama, T., and Otagiri, M.
  • Journal Title: Am. J. Physiol(Renal Physiol.) 295
  • NAID: 120005952926
  • Peer Reviewed
• [Journal Article] Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure (2008)
  • Author(s): Nonoguchi, H., Kiyama, S., Kitamura, K., Naruse, M., Tomita, M., Tazoe, N., Tajiri, M., Nakayama, Y., Kohda, Y., Inoue, T., and Tomita, K.
  • Journal Title: Hypertens Res. 31 Pages: 29-36
  • NAID: 10021260933
  • Peer Reviewed
• [Journal Article] Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATvl (SLC2A9) in humans (2008)
  • Author(s): Anzai, N., et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 26834-26838
  • Peer Reviewed
• [Journal Article] CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products (2008)
  • Author(s): Iwao, Y., et al.
  • Journal Title: Am. J. Physiol. (Renal Physiol. ) 295
  • Peer Reviewed
• [Journal Article] Effect of intravenous iron administration frequency on oxidative stress in chronic hemodialysis patients (2008)
  • Author(s): Anraku, M., et al.
  • Journal Title: Clin. Biochem. 41 Pages: 1168-1174
  • Peer Reviewed
• [Journal Article] Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure (2008)
  • Author(s): Nonoguchi, H., et. al.
  • Journal Title: Hypertens. Res. 31 Pages: 26-39
  • Peer Reviewed
• [Journal Article] An oral adsorbent, AST-120 protects against the progression of oxidative stress by reducing the accumulation of indoxyl sulfate in the systemic circulation in renal failure (2007)
  • Author(s): Shimoishi, K., Anraku, M., Kitamura, K., Tasaki, Y., Taguchi, K., Hashimoto, M., Fukunaga, E., Maruyama, T., and Otagiri, M.
  • Journal Title: Pharm. Res 24 Pages: 1283-1289
  • NAID: 120005894409
  • Peer Reviewed
• [Journal Article] Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients (2007)
  • Author(s): Kadowaki, D., Anraku, M., Tasaki, Y., Kitamura, K., Wakamatsu, S., Tomita, K., Gebicki, J. M., Maruyama, T., and Otagiri, M.
  • Journal Title: Hypertens. Res. 30 Pages: 395-402
  • NAID: 10019537151
  • Peer Reviewed
• [Journal Article] An oral adsorbent,AST-120 protects against the progression of oxidative stress by reducing the accumulation of indoxyl sulfate in the systemic circulation in renal failure (2007)
  • Author(s): Shimoishi, K., et. al.
  • Journal Title: Pharm. Res. 24 Pages: 1283-1289
  • Peer Reviewed
• [Journal Article] Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients (2007)
  • Author(s): Kadowaki, D., et. al.
  • Journal Title: Hypertens. Res. 30 Pages: 395-402
  • Peer Reviewed
• [Presentation] Camostat mesilate attenuates hypertension and kidney injury in Dahl salt-sensitive rats (2008)
  • Author(s): Kakizoe, Y., et.al.
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] プロテアーゼとプロテアーゼインヒビターの相互作用による生体Na代謝制御の分子基盤 (2007)
  • Author(s): 北村健一郎
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: アクトシティ浜松
  • Year and Date: 2007-05-25
• [Book] 医学のあゆみ (2007)
  • Author(s): 北村健一郎
  • Total Pages: 4
  • Publisher: 医歯薬出版株式会社
• [Book] 医学のあゆみ (2007)
  • Author(s): 北村 健一郎
  • Total Pages: 4
  • Publisher: 医歯薬出版株式会社