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

2011 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 平安女学院大学, 文化創造センター, 客員教授 (30177993) ; 芦原 英司 京都府立医科大学, 医学研究科, 講師 (70275197) ; 細木 誠之 京都府立医科大学, 医学研究科, 助教 (30405261)
• Keywords: ENaC / アルデステン / 皮質集合管 / プロテアーゼ阻害剤 / 浸透圧 / 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)の発現が促進されることをウエスタンブロッティング法を用いて確認した。この結果、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にした。
2)上記の結果、アルドステロン投与によりENaCのクリベッジが促進され、リサイクル効率を増大させることを明らかにした。

Research Products

• [Journal Article] Blockade of chloride ion transport enhances the cytocidal effect of hypotonic solution in gastric cancer cells (2012)
  • Author(s): Iitaka D, Shiozaki A, Ichikawa D, Kosuga T, Komatsu S, Okamaoto K, Fujiwara H, Ishii H, Nakahari T, Marunaka Y, Otsuji E
  • Journal Title: J Surgical Res Volume: 176(2) Pages: 524-534
  • Peer Reviewed
• [Journal Article] Hypotonic stress upregulates beta- and gamma-ENaC expression through suppression of ERK by inducing MKP-1 (2012)
  • Author(s): Niisato N, Ohta M, Eaton DC, Marunaka Y
  • Journal Title: Am J Physiol (Renal Physiol) Volume: 303(2) Pages: 240-252
  • Peer Reviewed
• [Journal Article] Pleural lavage with distilled water during surgery for esophageal squamous cell carcinoma (2011)
  • Author(s): Kosuga T, Shiozaki A, Ichikawa D, Fujiwara H, Kotnatsu S, Iitaka D, Tsujiura M, Morimura R, Takeshita H, Nagata H, Okamoto K, Nakahari T, Marunaka Y, Otsuji E
  • Journal Title: Oncolgy Reports Volume: 26 Pages: 577-586
  • Peer Reviewed
• [Journal Article] Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na+/K+/2Cl-cotransporter (2011)
  • Author(s): Nakajima K, Niisato N, Marunaka Y
  • Journal Title: Cell Physiol Biochem Volume: 28 Pages: 351-356
  • Peer Reviewed
• [Journal Article] Genistein enhances the NGF-induced neurite outgrowth (2011)
  • Author(s): Nakajima K, Niisato N, Marunaka Y
  • Journal Title: Biomed Res Volume: 32(5) Pages: 351-356
  • Peer Reviewed
• [Journal Article] Regulation of epithelial sodium transport via epithelial Na^+ channel (ENaC) (2011)
  • Author(s): Marunaka Y, Niisato N, Taruno A, Ohta M, Miyazaki H, Hosogi S, Nakajima K, Kusuzaki K, Ashihara E, Nishio K, Iwasaki Y, Nakahari T, Kubota T
  • Journal Title: J Biomed Biotechnol Volume: 2011 Pages: 978196
  • DOI: doi:10.1155/2011/978196
  • Peer Reviewed
• [Presentation] Recycling rates of ENaC depend on the total amount of recycled channels (2012)
  • Author(s): Marunaka Y, Taruno A
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Matsumoto
  • Year and Date: 20120329-31
• [Presentation] p-38-dependent suppression of ENaC endocytosis is involved in stimulation of Na^+ reabsorption by aldosterone in renal epithelial A6 cells (2012)
  • Author(s): Niisato N, Ohta M, Marunaka Y
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Matsumoto
  • Year and Date: 20120329-20120331
• [Presentation] Analysis of epithelial ion transport by mathematical model (2012)
  • Author(s): Sasamoto Kouhei, Niisato Naomi, Marunaka Yoshinori
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Matsumoto
  • Year and Date: 20120329-20120331
• [Presentation] The mechanisms of Na^+/H^+ exchanger inhibitor on proliferation of gastric cancer cells with several pathways (2012)
  • Author(s): Hosogi Shigekuni, Ohta Mariko, Nakajima Ken-ichi, Ashihara Eishi, Niisato Naomi, Marunaka Yoshinori
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Matsumoto
  • Year and Date: 20120329-20120331
• [Presentation] Measurement of intracellular chloride concentration in differentiating PC12 cells (2012)
  • Author(s): Nakajima Ken-ichi, Niisato Naomi, Marunaka Yoshinori
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Matsumoto
  • Year and Date: 20120329-20120331
• [Presentation] アルドステロンはp38依存的なENaCエンドサイトーシスを介してNa^+再吸収を制御する (2011)
  • Author(s): 新里直美、太田麻利子、丸中良典
  • Organizer: 2011年度生理学研究所研究会「上皮細胞の恒常性維持機構におけるイオン・物資輸送の新しい分子生理」
  • Place of Presentation: 岡崎
  • Year and Date: 20111121-20111122
• [Presentation] プロカテロール刺激時PDE1によるマウス細気管支線毛運動の周波数と振幅の調節 (2011)
  • Author(s): 中張隆司、丸中良典
  • Organizer: 2011年度生理学研究所研究会「上皮細胞の恒常性維持機構におけるイオン・物資輸送の新しい分子生理」
  • Place of Presentation: 岡崎
  • Year and Date: 20111121-20111122
• [Presentation] An inhibitor of Na^+/H^+ exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the intracellular Cl^- concentration via DIDS-sensitive pathway (2011)
  • Author(s): Hosogi S, Ashihara E, Niisato N, Kusuzaki K, Marunaka Y
  • Organizer: The 2nd Symposium of the International Society for Proton Dynamics in Cancer 2011
  • Place of Presentation: Nice
  • Year and Date: 20111118-20111119
• [Presentation] Hypotonicity-induced upregulation of beta- and gamma-ENaC expression through suppression of ERK by inducing MKP-1 (2011)
  • Author(s): Marunaka Y, Niisato N, Ohta M
  • Organizer: The 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels : Molecular Mechanisms and Pathophysiology. American Physiological Society
  • Place of Presentation: Pacific Grove(招待講演)
  • Year and Date: 20110918-20110922
• [Presentation] Involvement of p38-mecliated endocytosis in aldosterone-stimulated Na+ reabsorption in renal epithelial A6 cells (2011)
  • Author(s): Niisato N, Ohata M, Marunaka Y
  • Organizer: The 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels : Molecular Mechanisms and Pathophysiology. American Physiological Society
  • Place of Presentation: Pacific Grove
  • Year and Date: 20110918-20110922
• [Presentation] Dependence of ENaC recycling rate on the total amount of recycled channels (2011)
  • Author(s): Taruno A, Marunaka Y
  • Organizer: The 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels : Molecular Mechanisms and Pathophysiology. American Physiological Society
  • Place of Presentation: Pacific Grove
  • Year and Date: 20110918-20110922
• [Presentation] Hypotonic stress up-regulates Na+ reabsorption through MKP-1-mediated dephosphorylation in renal epithelial A6 cells (2011)
  • Author(s): Niisato N, Ohta M, Marunaka Y
  • Organizer: The 5th International Congress on Stress Response in Biology and Medicine
  • Place of Presentation: Quebec City
  • Year and Date: 20110821-20110825
• [Presentation] アルドルテロンによるp38/Akt依存的なナトリウム再吸収制御 (2011)
  • Author(s): 新里直美、西尾恭介、丸中良典
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20110615-20110617
• [Presentation] 大豆ゲニステインによる免疫細胞活性化 (2011)
  • Author(s): 丸中良典、芦原英司、新里直美、太田麻利子
  • Organizer: 第14回研究報告会(平成22年度助成課題)
  • Place of Presentation: 大阪
  • Year and Date: 20110530-20110531
• [Presentation] Regulatory Mechanism of Epithelial Na^+ Channel (ENaC) (2011)
  • Author(s): Marunaka, Y
  • Organizer: Institute of Developmental Biology and Cancer Research, University of Nice
  • Place of Presentation: Nice(招待講演)
  • Year and Date: 2011-11-17
• [Presentation] イオン環境依存性癌細胞増殖機構 (2011)
  • Author(s): 丸中良典
  • Organizer: 第1回癌イオノミクス研究会
  • Place of Presentation: 京都
  • Year and Date: 2011-11-05
• [Presentation] Regulatory mechanisms of cancer cell growth by ionic environments. International Symposium on Cancer Research (2011)
  • Author(s): Marunaka, Y
  • Organizer: Italy/Japan Joint Meeting on Cancer Research
  • Place of Presentation: Kyoto(招待講演)
  • Year and Date: 2011-11-04
• [Presentation] 神経突起伸張におけるK+/Cl-共輸送体の役割 (2011)
  • Author(s): 中島謙一、永尾光、新里直美、久育男、丸中良典
  • Organizer: 日本生理学会第104回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-01
• [Presentation] 管腔側膜上ENaC発現制御におけるp38の役割 (2011)
  • Author(s): 太田麻利子、新里直美、丸中良典
  • Organizer: 日本生理学会第104回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-01
• [Presentation] 胃癌細胞株MKN-28細胞株のおけるNa+/H+ exchanger (NHE)阻害剤の細胞内pH・Cl-濃度の与える影響と細胞増殖抑制機構 (2011)
  • Author(s): 細木誠之、太田麻利子、中島謙一、宮崎裕明、芦原英司、楠崎克之、新里直美、丸中良典
  • Organizer: 日本生理学会第104回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-01
• [Presentation] クロライドイオン輸送体活性化による神経突起伸長促進機構の解明 (2011)
  • Author(s): 丸中良典、楠崎克之、新里直美、芦原英司、中島謙一、細木誠之、羽柴光起
  • Organizer: ソルト・サイエンス研究財団第23回助成研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-19
• [Presentation] 気道上皮Calu-3細胞でのFisetinによるアニオン分泌制御 (2011)
  • Author(s): 新里直美、丸中良典
  • Organizer: 第10回肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-25
• [Presentation] マウス細気管支線毛運動における周波数と振幅の調節 (2011)
  • Author(s): 中張隆司、丸中良典
  • Organizer: 第5回iPUC-II (Integrated Pulmonary Circulation Research-II)
  • Place of Presentation: 東京
  • Year and Date: 2011-06-25