The role of Hippo-YAP pathway in alcohol-induced cardiac dysfunction

• Project/Area Number: 15H06182
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Legal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Noritake Kanako 東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (40758067)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: エタノール / 心筋細胞傷害 / Hippo-YAP経路 / 細胞間接着 / 心筋障害 / 細胞間接着分子

Outline of Final Research Achievements

Excessive alcohol consumption often causes compromised myocardial contractile function, although the precise mechanism remains unknown. We reported previously that when mouse atrium-derived HL-1 cardiomyocytes undergo apoptosis upon direct exposure to ethanol, the cellular cytoskeleton is severely disrupted and the anti-apoptotic transcriptional co-activator YAP is inactivated. The restoration of YAP activation rescues the cells from apoptosis: both the expression of constitutively active YAP and the stabilization of the actomyosin cytoskeleton prevent ethanol-induced cell death. Thus, a decrease in actin tension and YAP inactivation should be crucially involved in the cytotoxicity of ethanol on HL-1 cardiomyocytes.

Research Products

• [Journal Article] 差分解説：アルコールによる心障害 (2017)
  • Author(s): 則竹香菜子, 上村公一
  • Journal Title: 日本医事新報 Volume: 印刷中
• [Journal Article] Direct Exposure to Ethanol Disrupts Junctional Cell-Cell Contact and Hippo-YAP Signaling in HL-1 Murine Atrial Cardiomyocytes. (2015)
  • Author(s): Noritake K, Aki T, Funakoshi T, Unuma K, Uemura K.
  • Journal Title: PLoS One Volume: 10(8) Issue: 8 Pages: e0136952-e0136952
  • DOI: 10.1371/journal.pone.0136952
  • Peer Reviewed / Open Access
• [Journal Article] アルコールによる心筋障害と オートファジーの役割 (2015)
  • Author(s): 則竹香菜子，秋利彦， 上村公一
  • Journal Title: 月刊「細胞」 Volume: 47(14) Pages: 44-47
• [Presentation] HL-1心筋細胞においてエタノールは細胞間接着・細胞骨格を破綻し、Hippo経路の機能を障害する (2015)
  • Author(s): 則竹香菜子，秋 利彦，上村公一
  • Organizer: 第88回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-03
• [Presentation] アルコールの毒性と心筋細胞障害 (2015)
  • Author(s): 則竹香菜子，秋 利彦，上村公一
  • Organizer: 第50回日本アルコール・薬物医学会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-10-12
  • Invited