The analysis of molecular mechanism of Meniere disease based on the cellular stress response of endolymphatic sac cell

• Project/Area Number: 25861598
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Nihon University
• Principal Investigator: MASUDA Takeshi 日本大学, 医学部, 助教 (60625218)
• Research Collaborator: TSUCHIHASHI Nana
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内耳 / 小胞体 / オートファジー / 内耳培養細胞 / 小胞体ストレス応答 / IP3R / LC3-II

Outline of Final Research Achievements

The cell viability after treatment of Tunicamycin was decreased in dose- and time- dependent manner. Ｗe defined this condition as the model of ER stress-induced auditory cell death. The findings that injured mitochondria surrounded by autophagosomes were confirmed under TEM. The expression of LC3-II was time-dependently increased in Tunicamycin-treated cells. These results mean that autophagy was consistently induced in Tunicamycin-treated cells. The expression of IP3R and CHOP was decreased after peaking at 12 hours after the treatment of Tunicamycin. The expression of BDNF and CAPS2 was time-dependently decreased in Tunicamycin-treated cells. The expression of Bcl-2 and Beclin1 was decreased in Tunicamycin-treated cells. The expression of Atoh1 and Myosin VIIA after treatment of Tunicamycin was time-dependently decreased. Our results lead to the suggestion that there is a signaling cross talk between ER stress response, IP3R activity through BDNF and autophagy in auditory cells.

Research Products

• [Presentation] H2O2 treatment accelerates autophagy and cellular senescence in auditory cell line (2014)
  • Author(s): Tsuchihashi Nana Akagi, Hayashi Ken, Goto Fumiyuki, Yasuyuki Nomura, Takeshi Masuda, Fujioka Masato, Kanzaki Sho, Ogawa Kaoru
  • Organizer: Inner Ear Biology Workshop
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-11-01 – 2014-11-04
• [Presentation] Molecular mechanism of tinnitus from the standpoint of autophagy in auditory cells. (2014)
  • Author(s): Ken Hayashi, Fumiyuki Goto, Nana Tsuchihashi, Yasuyuki Nomura, Takeshi Masuda, Masato Fujioka, Sho Kanzaki, Kaoru Ogawa
  • Organizer: Korea-Japan Joint Meeting of Otoryhinolaryngology Head and Neck Surgery
  • Place of Presentation: ソウル(韓国）
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] Molecular mechanism of tinnitus from the standpoint of autophagy (2013)
  • Author(s): Ken Hayashi, Fumiyuki Goto, Nana Tsuchihashi, Yasuyuki Nomura, Takeshi Masuda, Masato Fujioka, Sho Kanzaki, Kaoru Ogawa
  • Organizer: 第23回日本耳科学会学術講演会 English Session
  • Place of Presentation: 宮崎