アルドステロンによるENaC異常調節に起因する体液量感受機構破綻の分子メカニズム

2007 Fiscal Year Annual Research Report

• Project/Area Number: 17390057
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 丸中 良典 Kyoto Prefectural University of Medicine, 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) ; 宮崎 裕明 京都府立医科大学, 医学研究科, 助教 (30360027) ; 中島 謙一 京都府立医科大学, 医学研究科, 助教 (40398392)
• Keywords: 上皮型ナトリウムチャネル / アルドステロン / 高血圧 / 腎尿細管 / 腎集合管 / 細胞内トラッフィッキング / 浸透圧 / SGK1

Research Abstract

アルデステロンが細胞内ENaCの細胞内における存在部位移動速度および存在部位の変化をもたらすことが明らかとなった。腎遠位部尿細管モデル細胞において、アルドステロン非処理の細胞においては、多くのENaCはゴルジ装置に存在し、アルドステロン刺激により産生されたENaCの多くはERに存在することが明らかとなった。さらには、アルドステロン管腔側膜上から細胞内へのENaC取り込み速度を低下させ、一方細胞内から管腔側膜上への移動速度には変化を及ぼさないことを明らかとした。また、浸透圧上昇により、ENaCの管腔側膜上から細胞内へ取り込み速度が上昇し、この細胞内に取り込まれたENaCは、ERへのリサイクルされることも明らかとなった。
24時間に渡る低浸透圧負荷は、ENaCのbeta/gamma mRNA発現を増強させることを明らかにした。さらには、これらのmRNAの発現増強に係わるシグナルとして、p38が関与しているを示した。
浸透圧変化によるENaC遺伝子発現制御、またENaCタンパクの細胞内移動制御に係わるSGK1遺伝子発現制御に細胞内カルシウムイオンが関与していることも明らかした。

Research Products

• [Journal Article] Regulation of the paracellular Na+ and Cl- conductances by the NaC1-generated osmotic gradient in a manner dependent on the direction of osmotic gradients. (2008)
  • Author(s): Tokuda S, Niisato N, Nakajima K, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 366(2) Pages: 464-70
  • Peer Reviewed
• [Journal Article] Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells. (2008)
  • Author(s): Miyazaki H, Shiozaki A, Niisato N, Ohsawa R, Itoi H, Ueda Y, Otsuji E, Yamagishi H, Iwasaki Y, Nakano T, Nakahari T, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 366(2) Pages: 506-12
  • Peer Reviewed
• [Journal Article] Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells. (2008)
  • Author(s): Taruno A, Niisato N, Marunaka Y.
  • Journal Title: Am J Physiol Renal Physiol. 294(1) Pages: F177-86
  • Peer Reviewed
• [Journal Article] Regulation of paracellular ion conductances by NaC1 gradients in renal epithelial cells. (2007)
  • Author(s): Tokuda S, Niisato N, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 363(3) Pages: 566-571
  • Peer Reviewed
• [Journal Article] Epithelial Na+ channel and ion transport in human nasal polyp and paranasal sinus mucosa. (2007)
  • Author(s): Yasuda M, Niisato N, Miyazaki H, Iwasaki Y, Hama T, Dejima K, Hisa Y, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 362(3) Pages: 753-758
  • Peer Reviewed
• [Journal Article] Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells. (2007)
  • Author(s): Maki M, Miyazaki H, Nakajima K, Yamane J, Niisato N, Morihara T, Kubo T, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 361(4) Pages: 1038-1043
  • Peer Reviewed
• [Journal Article] Aldosterone-induced modification of osmoregulated ENaC trafficking. (2007)
  • Author(s): Niisato N, Taruno A, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 361(1) Pages: 162-168
  • Peer Reviewed
• [Journal Article] HCO_3-dependent pH_i recovery and overacidification induced by NH_4^+ pulse in rat lung alveolar type II cells: HCO_3^-dependent NH_3 excretion from lungs? (2007)
  • Author(s): Tokuda S, Shimamoto C, Yoshida H, Murao H, Kishima G, Ito S, Kubota T, Hanafusa T, Sugimoto T, Niisato N, Marunaka Y, Nakahari T.
  • Journal Title: Pflugers Arch. 455(2) Pages: 223-239
  • Peer Reviewed
• [Journal Article] Essential role of NKCC1 in NGF-induced neurite outgrowth. (2007)
  • Author(s): Nakajima K, Miyazaki H, Niisato N, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 359(3) Pages: 604-610
  • Peer Reviewed
• [Journal Article] An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury. (2007)
  • Author(s): Ohsugi S, Iwasaki Y, Takemura Y, Nagata K, Harada H, Yokomura I, Hosogi S, Yuba T, Niisato N, Miyazaki H, Matsubara H, Fushiki S, Marunaka Y.
  • Journal Title: Biomed Res. 28(2) Pages: 91-99
  • Peer Reviewed
• [Journal Article] Involvement of p38 MAPK in hypotonic stress-induced stimulation of beta-and gamma-ENaC expression in renal epithelium. (2007)
  • Author(s): Niisato N, Taruno A, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun. 358(3) Pages: 819-824
  • Peer Reviewed
• [Journal Article] Abnormal expression of ENaC and SGK1 mRNA induced by dietary sodium in Dahl salt-sensitively hypertensive rats. (2007)
  • Author(s): Aoi W, Niisato N, Sawabe Y, Miyazaki H, Tokuda S, Nishio K, Yoshikawa T, Marunaka Y.
  • Journal Title: Cell Biol Int. 31(10) Pages: 1288-1291
  • Peer Reviewed
• [Journal Article] Action of neltenexine on anion secretion in human airway epithelia. (2007)
  • Author(s): Niisato N, Hasegawa I, Tokuda S, Taruno A, Nakajima K, Miyazaki H, Iwasaki Y, Marunaka Y.
  • Journal Title: Biochem Biophys Res Commun 356(4) Pages: 1050-1055
  • Peer Reviewed
• [Journal Article] Hypotonicity stimulates renal epithelial sodium transport by activating JNK viareceptor tyrosine kinases. (2007)
  • Author(s): Taruno A, Niisato N, Marunaka Y.
  • Journal Title: Am J Physiol Renal Physiol. 293(1) Pages: F128-F138
  • Peer Reviewed
• [Journal Article] Physiological significance of hypotonicity-induced regulatory volume decrease: reduction in intracellular Cl-concentration acting as an intracellular signaling. (2007)
  • Author(s): Miyazaki H, Shiozaki A, Niisato N, Marunaka Y.
  • Journal Title: Am J Physiol Renal Physiol. 292(5) Pages: F1411-F1417
  • Peer Reviewed
• [Presentation] Intracellular chloride-dependent modulation of aldosterone action on Na^+reabsorption. (2007)
  • Author(s): Niisato N, Marunaka Y.
  • Organizer: Aldosterone and ENaC: from Gene to Disease
  • Place of Presentation: Zermatt, Switzerland
  • Year and Date: 20071003-07
• [Presentation] Regulation of ENaC function by hypotonic stress in renal epithelial A6 cells: genomic and non-genomic mechanisms. (2007)
  • Author(s): Taruno A, Niisato N, Marunaka Y.
  • Organizer: Aldosterone and ENaC: from Gene to Disease
  • Place of Presentation: Switzerland
  • Year and Date: 20071003-07