Regulation of the OHC cytoskeleton induced by lipid raft.-Effects of cholesterol alterations on hearing-

• Project/Area Number: 22390315
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yamagata University
• Principal Investigator: KAKEHTA Seiji 山形大学, 医学部, 教授 (90261619)
• Co-Investigator(Kenkyū-buntansha): UENO Shinya 弘前大学, 医学(系)研究科, 教授 (00312158) ; WADA Hiroshi 東北大学, 工学(系)研究科, 教授 (30111264) ; MURAKOSHI Michio 東北大学, 大学院・工学研究科, 助教 (70570901) ; MARUYA Shinithiro 国際医療福祉大学, 大学病院, 講師 (90396408)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 内耳 / パッチクランプ法 / 細胞内シグナル伝達系 / 外有毛細胞 / 運動能 / キャパシタンス / Lipid raft / 細胞骨格 / G蛋白

Research Abstract

Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by M.CD or water-soluble cholesterol affect the stiffness, capacitance, motility and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. As a result, internally perfused GTP.S (agonist of G proteins) inhibited the M.CD effects and GDP.S (antagonist of G proteins) inhibited the cholesterol effects, indicating that cytoskeletal reconstruction of OHCs might be induced by cholesterol alteration through intracellular signaling pathways involving G proteins.

Research Products

• [Journal Article] Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells (2013)
  • Author(s): Nagaki T, Kakehata S, Kitani R, Abe T, Shinkawa H.
  • Journal Title: Pflugers Archiv -European Journal of Physiology
  • Peer Reviewed
• [Journal Article] Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells (2013)
  • Author(s): Nagaki T
  • Journal Title: Pflugers Archiv - European Journal of Physiology Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Motile responses of cochlear outer hair cells stimulated with an alternating electrical field (2011)
  • Author(s): Kitani R, Kakehata S, Kalinec F.
  • Journal Title: Hear Res Volume: 280(1-2) Pages: 209-18
  • Peer Reviewed
• [Journal Article] Motile responses of cochlear outer hair cells stimulated with an alternating electrical field (2011)
  • Author(s): Kitani, Kakehata, Kalinec
  • Journal Title: Hearing Research Volume: 280 Pages: 209-218
  • Peer Reviewed
• [Presentation] G蛋白を介した細胞内シグナル伝達系が蝸牛外有毛細胞膜の脂質変化に及ぼす効果 (2010)
  • Author(s): 長岐孝彦
  • Organizer: 第20回日本耳科学会
  • Place of Presentation: 愛媛県松山市、ひめぎんホール
  • Year and Date: 2010-10-07
• [Presentation] G蛋白を介した細胞内シグナル伝達系が蝸牛外有毛細胞膜の脂質変化に及ぼす効果 (2010)
  • Author(s): 長岐孝彦
  • Organizer: 第20回日本耳科学会
  • Place of Presentation: 愛媛県松山市
  • Year and Date: 2010-10-07