Role of intracellular degradation systems in genesis of heart failure

• Project/Area Number: 21390240
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: OTSU Kinya 大阪大学, 医学系研究科, 准教授 (20294051)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Osamu 大阪大学, 大学院・医学系研究科, 助教 (90467580) ; HIKOSO Shungo 大阪大学, 大学院・医学系研究科, 助教 (30423164)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 細胞内分解系 / 心不全 / 細胞死 / 心筋細胞死

Research Abstract

In this study, we examined the role of degradation systems in the genesis of heart failure. Our results indicate that calpain plays a cardioprotective role and autophagy is important to maintain cardiac function during aging. Furthermore, DNase II regulates inflammatory responses in the heart by degrading mitochondrial DNA.

Research Products

• [Journal Article] Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure (2012)
  • Author(s): 岡崇史、彦惣俊吾、山口修、種池学、武田理宏、玉井敬人、大藪丈太、村川智一、中山博之、西田和彦、審良静男、山本章次、小室一成、大津欣也
  • Journal Title: Nature Volume: (in press)
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure (2012)
  • Author(s): Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K
  • Journal Title: Nature Volume: 485 Issue: 7397 Pages: 251-255
  • DOI: 10.1038/nature10992
  • Peer Reviewed
• [Journal Article] Calpain protects the heart from hemodynamic stress (2011)
  • Author(s): 種池学、溝手勇、森田孝、渡部徹也、彦惣俊吾、山口修、武田理宏、岡崇史、玉井敬人、大藪丈太、村川智一、中山博之、西田和彦、竹田潤二、望月直樹、小室一成、大津欣也
  • Journal Title: The Journal of Biological Chemistory Volume: 286 Pages: 32170-7
  • Peer Reviewed
• [Journal Article] Calpain protects the heart from hemodynamic stress (2011)
  • Author(s): 種池学、山口修, ほか
  • Journal Title: Journal of Biological Chemistry Volume: 286 Issue: 37 Pages: 32170-32177
  • DOI: 10.1074/jbc.m111.248088
  • Peer Reviewed
• [Journal Article] Inhibition of autophagy in the heart induces age-related cardiomyopathy (2010)
  • Author(s): 種池学、山口修、中井敦子、彦惣俊吾、武田理宏、溝手勇、岡崇史、玉井敬人、大藪丈太、村川智一、西田和彦、清水孝彦、堀正二、小室一成、白澤卓司、水島昇、大津欣也
  • Journal Title: Autophagy Volume: 6 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes (2009)
  • Author(s): 大宮茂幹, ほか
  • Journal Title: Journal of Molecular and Cellular Cardiology 46 Pages: 59-66
  • Peer Reviewed
• [Journal Article] The IκB kinase β/NF-κB signaling pathway protects the heart from hemodynamic stress mediated through the regulation of MnSOD expression (2009)
  • Author(s): 彦惣俊吾, ほか
  • Journal Title: Circulation Research 105 Pages: 70-9
  • Peer Reviewed
• [Presentation] Molecular link between cell death and sterile inflammation (2012)
  • Author(s): 大津欣也
  • Organizer: ヨーロッパ心不全学会冬季研究学会
  • Place of Presentation: スイス
  • Year and Date: 2012-01-19
• [Presentation] The molecular link between cell death and sterile inflammation (2012)
  • Author(s): 大津欣也
  • Organizer: 7the Annual Winter Research Meeting on Translational Basic Science
  • Place of Presentation: ル リアブレレッツ、スイス(招待講演)
  • Year and Date: 2012-01-19
• [Presentation] Inflammation and autophagy (2011)
  • Author(s): 大津欣也
  • Organizer: 基礎心臓病学カンファレンス、ラスベガス
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2011-07-19
• [Presentation] Inflammation and autophagy (2011)
  • Author(s): 大津欣也
  • Organizer: Basic Cardiovascular Sciences 2011 Scientific Sessions
  • Place of Presentation: ニューオーリンズ、アメリカ合衆国(招待講演)
  • Year and Date: 2011-07-19
• [Presentation] Lysosomal DNaseII Digests Mitochondrial DNA Through Lysosome/ Autophagy System to Maintain Cardiac Function in Pressured-Overloaded Hearts (2010)
  • Author(s): 岡崇史
  • Organizer: 米国心臓学会
  • Place of Presentation: シカゴ、アメリカ合衆国
  • Year and Date: 2010-11-10
• [Presentation] 血行動態負荷並びに老化における心筋細胞オートファジーの役割 (2010)
  • Author(s): 山口修
  • Organizer: 第14回日本心不全学会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-10
• [Presentation] Autophagy as an adaptive mechanism to cardiac stress (2010)
  • Author(s): 大津欣也
  • Organizer: XXth World Congress of the International Society for Heart Research
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2010-05-15
• [Presentation] Constitutive Autophagy is Necessary for Maintenance of Cardiac Structure and Function in Aged mouse Hearts (2010)
  • Author(s): 種池学
  • Organizer: 第10回国際心臓研究学会世界大会
  • Place of Presentation: 京都
  • Year and Date: 2010-05-10
• [Presentation] The in vivo Role of IKKb/NF-kB Signaling Pathway in the Heart (2009)
  • Author(s): 彦惣俊吾, 他
  • Organizer: 第26回国際心臓研究学会日本部会
  • Place of Presentation: 札幌
  • Year and Date: 2009-12-02
• [Presentation] The in vivo Role of IKKb/ NF-kB Signaling Pathway in the Heart (2009)
  • Author(s): 彦惣俊吾
  • Organizer: 第26回国際心臓研究学会日本部会
  • Place of Presentation: 札幌
  • Year and Date: 2009-12-01
• [Presentation] 心筋細胞においてフェリチン重鎖の減少は遊離鉄および酸化ストレスの増加をもたらし細胞死を誘導する (2009)
  • Author(s): 大宮茂幹, 他
  • Organizer: 第19回日本循環薬理学会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-06
• [Presentation] MAPK Signaling and Regulation of Cardiac Hypertrophy (2009)
  • Author(s): 大津欣也
  • Organizer: 基礎心臓病学カンファレンス、ラスベガス
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2009-07-20
• [Presentation] Autophagy and apoptosis in heart disease (2009)
  • Author(s): 大津欣也
  • Organizer: ヨーロッパ心不全学会
  • Place of Presentation: ニース、フランス
  • Year and Date: 2009-05-20