プロテアーゼによるENaC細胞内局在制御メカニズムの解明

2010 Fiscal Year Annual Research Report

• Project/Area Number: 20390060
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 丸中 良典 京都府立医科大学, 医学研究科, 教授 (00127036)
• Co-Investigator(Kenkyū-buntansha): 新里 直美 京都府立医科大学, 医学研究科, 准教授 (00237645) ; 中島 謙一 京都府立医科大学, 医学研究科, 助教 (40398392) ; 楠崎 克之 京都府立医科大学, 医学研究科, 教授 (30177993) ; 芦原 英司 京都府立医科大学, 医学研究科, 講師 (70275197)
• Keywords: ENaC / アルデステン / 皮質集合管 / プロテアーゼ阻害剤 / 透浸圧 / トラッフィッキング / 高血圧 / ナトリウム輸送

Research Abstract

アルドステロンが、管腔側膜結合型プロテアーゼ発現・活性を亢進させることにより、ENaCの管腔側膜上滞在時間を増大させることを明らかにした。
1) アルドステロンの投与の有無により、管腔側膜結合型プロテアーゼ(channel activating protease : CAP)の発現が影響を受けるか否かをウエスタンブロッティングにより検討した。さらに、アルドステロンの投与の有無により、管腔側膜分画のプロテアーゼ(CAP)活性が影響を受けるか否かを調べた。その結果、アルドステロン投与により、CAPの発現および活性とも、増大することが明らかとなった。
2) アルドステロン投与のENaCリサイクル効率に及ぼす影響を、ENaCユビキチン化レベルについても併せて検討したところ、ENaCリサイクル率は増大し、一方ENaCユビキチン化レベルは減少することが明となった。
3) アルドステロン以外にENaCの膜発現量を増やすと考えられるcAMP刺激(細胞内トラッフィッキングを介して)による系では、ENaCの管腔側膜上の発現量は増大したが、ENaCユビキチン化には影響はなく、ENaCリサイクル効率は増大さることが明らかとなった。

Research Products

• [Journal Article] KF-1 Ubiquitin Ligase : Anxiety Suppressor Model. (2011)
  • Author(s): Hashimoto-Gotoh T, Iwabe N, Tsujimura A, Nakagawa M, Marunaka Y.
  • Journal Title: Cell Biochem Biophys Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Photodynamic therapy with acridine orange in musculoskeletal sarcomas. (2010)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Marunaka Y, Hosogi S, Uchida A, Sudo A.
  • Journal Title: J Bone Joint Surg Br. Volume: 92(6) Pages: 760-762
  • Peer Reviewed
• [Journal Article] Peroxisome proliferation activation receptor alpha modulation of Ca^<2+>-regulatedexocytosis via arachidonic acid in guinea-pig antral mucous cells. (2010)
  • Author(s): Sawabe Y, Shimamoto C, Sakai A, Kuwabara H, Saad AH, Nakano T, Takitani K, Tamai H, Mori H, Marunaka Y, Nakabari T
  • Journal Title: Exp Physiol. Volume: 95(8) Pages: 858-868
  • Peer Reviewed
• [Journal Article] Photodynamic therapy with acridine orangein musculoskeletal sarcomas. (2010)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Marunaka Y, Hosogi S, Uchida A, Sudo A.
  • Journal Title: J Bone Joint Surg (Br). Volume: 92(6) Pages: 760-762
  • Peer Reviewed
• [Journal Article] Analysis of blocker-labeled channels reveals the dependence of recycling rates of ENaC on the total amount of recycled channels (2010)
  • Author(s): Taruno A, Marunaka Y.
  • Journal Title: Cell Phsyiol Biochem. Volume: 26(6) Pages: 925-934
  • Peer Reviewed
• [Presentation] Flavonoids stimulate NGF-induced neurite outgrowth in PC12 cells via activation of Na^+/K^+/2Cl^- cotransporter. (2010)
  • Author(s): Nakajima K, Niisato N, Marunaka Y.
  • Organizer: The 2010 International Chemical Congress of Pacific Basin Societies.
  • Place of Presentation: Hawaii
  • Year and Date: 20101215-20101220
• [Presentation] Flavonoids stimulate NKCC-mediated Cl- secretion in human airway epithelial Calu-3 cells. (2010)
  • Author(s): Niisato N, Marunaka Y.
  • Organizer: The 2010 International Chemical Congress of Pacific Basin Societies.
  • Place of Presentation: Hawaii
  • Year and Date: 20101205-20101220
• [Presentation] Morphological alterations of cell membrane during apoptosis induced by photodynamic therapy with acridine orange. (2010)
  • Author(s): Kusuzaki K, Hosogi S, Ashihara E, Nakajima K, Niisato N, Marunaka Y.
  • Organizer: Membrane Symposium 2010
  • Place of Presentation: Kyoto
  • Year and Date: 20101119-20101120
• [Presentation] Chloride ion effect on cancer cells. (2010)
  • Author(s): Marunaka Y.
  • Organizer: Symposium on Advanced Biotechnologies & Instrumentations.
  • Place of Presentation: China
  • Year and Date: 20101023-20101024
• [Presentation] Na^+/H^+ exchanger isoform 1 (NHE-1)-dependent proliferation of gastric cancer cells. (2010)
  • Author(s): Hosogi S, Kusuzaki K, Niisato N, Marunaka Y.
  • Organizer: The 1^<st> Symposium of the International Society for Proton Dynamics in Cancer.
  • Place of Presentation: Rome
  • Year and Date: 20100927-20100928
• [Presentation] Translational research of photodynamic therapy with acridine orange which targets acidic vesicles and environment of cancer cells. (2010)
  • Author(s): Kusuzaki K, Hosogi S, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Sudo A, Marunaka Y.
  • Organizer: The 1^<st> Symposium of the International Society for Proton Dynamics in Cancer.
  • Place of Presentation: Rome
  • Year and Date: 20100927-20100928
• [Presentation] クロライドイオンによる癌細胞増殖制御メカニズム (2010)
  • Author(s): 丸中良典
  • Organizer: 第34回近畿肉腫研究会
  • Place of Presentation: 三重
  • Year and Date: 20100724-20100725
• [Presentation] Regulatory mechanism of Cl^-secretion by flavonoid in human airway epithelial Calu-3 cells. (2010)
  • Author(s): Niisato N, Marunaka Y.
  • Organizer: The 87^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Morioka
  • Year and Date: 20100519-20100521
• [Presentation] Cholinergic regulation of epithelial Na^+ channel (ENaC) in alveolar type 2 cell. (2010)
  • Author(s): Takemura Y, Helms My N, Eaton Douglas C, Marunaka Y.
  • Organizer: The 87^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Morioka
  • Year and Date: 20100519-20100521
• [Presentation] Flavonoids stimulate NGF-induced neurite outgrowth in PC 12 cells via activation of Na^+/K^+/2Cl^- cotransporter. (2010)
  • Author(s): Nakajima K, Niisato N, Marunaka Y.
  • Organizer: The 87^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Morioka
  • Year and Date: 20100519-20100521
• [Presentation] Na^+/H^+ exchanger isoform 1(NHE-1)-dependent proliferation of gastric cancer cells (2010)
  • Author(s): Hosogi S, Nakajima K, Miyazaki H, Niisato N, Marunaka Y.
  • Organizer: The 87^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Morioka
  • Year and Date: 20100519-20100521
• [Presentation] The essential role of p38 in aldosterone action on ENaC-mediated Na^+ transport. (2010)
  • Author(s): Ohta M, Niisato N, Marunaka Y.
  • Organizer: The 87^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Morioka
  • Year and Date: 20100519-20100521
• [Presentation] β_2刺激によるマウス末梢気道線毛運動の活性化:高速度カメラを用いた観察 (2010)
  • Author(s): 中張隆司、大黒恵理子、丸中良典
  • Organizer: 肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-03