Effects of ceramide and sphingolipids on cochlear injury

• Project/Area Number: 24592541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: University of Tsukuba
• Principal Investigator: Tabuchi Keiji 筑波大学, 医学医療系, 講師 (80361335)
• Co-Investigator(Kenkyū-buntansha): 原 晃 筑波大学, 医学医療系, 教授 (10156474)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 内耳 / 蝸牛 / シスプラチン / 有毛細胞 / 耳毒性

Outline of Final Research Achievements

Ceramide and sphingosine increased cochlear injury induced by cisplatin. Ceramide and sphingosine themselves induced cochlear injury without cisplatin at high doses.On the other hand, ceramide-1-phosphate (C1P) decreased cochlear injury induced by cisplatin. Inhibition of ceramide kinase which converted ceramide to C1P significantly worsened cochlear injury induced by ceramide. Intrinsic cochlear ceramide kinase protected the cochlea against ototoxicity.

Research Products

• [Journal Article] The role of peroxiredoxin I in cisplatin-induced ototoxicity (2017)
  • Author(s): Le Q, Tabuchi K, Warabi E, Hara A
  • Journal Title: Auris Nasus Larynx Volume: 44 Pages: 205-212
• [Journal Article] Hair Cell Loss Induced by Sphingosine and a Sphingosine Kinase Inhibitor in the Rat Cochlea. (2016)
  • Author(s): Tani K, Tabuchi K, Hara A
  • Journal Title: Neurotoxicology Research Volume: 29 Issue: 1 Pages: 35-46
  • DOI: 10.1007/s12640-015-9563-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ceramide/sphingomyelin cycle involvement in gentamicin-induced cochlear hair cell death. (2015)
  • Author(s): Chi L, Tabuchi K, Nakamagoe M, Nakayama M, Hara A
  • Journal Title: Arch Toxicol Volume: 89 Issue: 3 Pages: 415-421
  • DOI: 10.1007/s00204-014-1259-x
  • NAID: 120007130316
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The influence of sphingosine-1-phosphate receptor antagonists on gentamicin-induced hair cell loss of the rat cochlea. (2014)
  • Author(s): Nakayama M, Tabuchi K,Hoshino T, Nakamagoe M, Nishimura B, Hara A
  • Journal Title: Neuroscience Letters Volume: 561 Pages: 91-95
  • DOI: 10.1016/j.neulet.2013.12.063
  • Peer Reviewed
• [Journal Article] The effects of A1 and A2A adenosine receptor agonists on kainic acid excitotoxicity in the guinea pig cochlea. (2012)
  • Author(s): Tabuchi K, Sakai S, Nakayama M, Nishimura B, Hayashi K, Hirose Y, Hara A
  • Journal Title: Neurosci Lett Volume: 518 Issue: 1 Pages: 60-63
  • DOI: 10.1016/j.neulet.2012.04.057
  • Peer Reviewed
• [Presentation] Hair Cell Loss Induced by Sphingosine and a Sphingosine Kinase Inhibitor in the Rat Cochlea. (2016)
  • Author(s): Tani K, Tabuchi K, Hara A
  • Organizer: 2015 ARO Midwinter meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2016-02-15
  • Int'l Joint Research
• [Presentation] Ceramide/sphingomyelin cycle involvement in gentamicin-induced cochlear hair cell death. (2015)
  • Author(s): Chi L, Tabuchi K, Hara A
  • Organizer: ARO midwinter meeting
  • Place of Presentation: Marriott Hotel Baltimore (Baltimore, USA)
  • Year and Date: 2015-02-21
• [Presentation] ゲンタマイシン耳毒性におけるスフィンゴ脂質代謝産物の影響 (2012)
  • Author(s): 西村文吾、田渕経司、中山雅博、中馬越真理子、Chi LNU、原 晃
  • Organizer: 第23回日本耳科学会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] ゲンタマイシン耳毒性における蝸牛外有毛細胞アポトーシスに対するスフィンゴシン1リン酸受容体アンタゴニストの影響 (2012)
  • Author(s): 中山雅博、田渕経司、西村文吾、中馬越真理子、原 晃
  • Organizer: 第112回日本耳鼻咽喉科学会
  • Place of Presentation: 朱鷺メッセ