Regulation of mitochondrial energetics and cell death by p53 and SCO2

• Project/Area Number: 19590825
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MATOBA Satoaki Kyoto Prefectural University of Medicine, 医学研究科, 助教 (10305576)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ミトコンドリア / p53 / エネルギー代謝 / アポトーシス / 心筋細胞 / 心不全 / 虚血性心疾患 / 脂肪酸代謝 / 解糖系

Research Abstract

p53により転写制御される細胞内シグナルとしてTIGAR(TP53-Induced Glycolysis and Apoptosis Regulator)及びミトコンドリアの構成蛋白であるSCO2(Synthesis of Cytochrome c Oxygenase 2)が、細胞のエネルギー代謝を調節しマウス、ラットを用いて虚血時における心筋の生存に関わっている事を発見証明した。この成果は、今後の臨床治療研究に結びつく。

Research Products

• [Journal Article] Endothelium-targeted overexpression of constitutively active FGF receptor induces cardioprotection in mice myocardial infarction (2009)
  • Author(s): Matsunaga S, Matoba S, et.al.
  • Journal Title: J Mol Cell Cardiol 46 Pages: 663-673
• [Journal Article] Cardiomyopathy in a Japanese family with the Glu61Lys transthyretin variant : a new phenotype (2009)
  • Author(s): Noto Y, Matoba S, et.al.
  • Journal Title: Amyloid 16 : 2 Pages: 99-102
  • NAID: 10025625608
• [Journal Article] Therapeutic angiogenesis for peripheral artery diseases by autologous bone marrow cell transplantation (2009)
  • Author(s): Matoba S, Matsubara H
  • Journal Title: Curr Pharm Design (in press)
• [Journal Article] TACT Follow-Up Study Investigators. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (TACT Trial) in patients with chronic limb ischemia (2008)
  • Author(s): Matoba S, Tatsumi T, et.al.
  • Journal Title: Am Heart J 156 Pages: 1010-1018
• [Journal Article] p53 is a new target to improve cardiac metabolism (2008)
  • Author(s): Kimata M, Matoba S, et.al.
  • Journal Title: Circ Res 103
• [Journal Article] Effects of Hospital Volume of Primary Percutaneous Coronary Interventions on Angiographic Results and In-Hospital Outcomes for Acute Myocardial Infarction (2008)
  • Author(s): Shiraishi J, Matoba S, et.al.
  • Journal Title: Circ J 72 Pages: 1041-1046
  • NAID: 110006792053
• [Journal Article] Predictors of In-Hospital Outcome After Primary Percutaneous Coronary Intervention for Recurrent Myocardial Infarction (2008)
  • Author(s): Shiraishi J, Matoba S, et.al.
  • Journal Title: Circ J 72 Pages: 1225-1229
  • NAID: 110006835719
• [Journal Article] 心血管難病に挑む再生医療 (2008)
  • Author(s): 的場聖明、高橋知三郎、松原弘明
  • Journal Title: 京都府立医科大学雑誌 117 : 10 Pages: 783-792
• [Journal Article] p53 is a new target to improve cardiac metabolism (2008)
  • Author(s): Masaki Kimata
  • Journal Title: Circulation research 103
  • Peer Reviewed
• [Journal Article] Pathogenesis of acute myocardial infarction in young male adults with or without obesity (2007)
  • Author(s): Shiraishi J, Matoba S, et.al.
  • Journal Title: J Cardiol 49 Pages: 13-21
  • NAID: 10018697032
• [Journal Article] A pivotal role for p53 : balancing aerobic respiration and glycolysis (2007)
  • Author(s): Ma W, Matoba S., et.al.
  • Journal Title: J Bioenerg Biomembr 39 Pages: 243-246
• [Journal Article] Intracoronary transplantation of non-expanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction (2007)
  • Author(s): Tatsumi T, Matoba S, et.al.
  • Journal Title: Circ J 71 Pages: 1199-1203
  • NAID: 110006368842
• [Journal Article] Obesity not associated with medium-term prognosis among Japanese male survivors hospitalized for acute myocardial infarction (2007)
  • Author(s): Shiraishi J, Matoba, S et.al.
  • Journal Title: J Cardio 50 Pages: 93-100
  • NAID: 10019863675
• [Journal Article] In-hospital outcomes of primary percutaneous coronary interventions performed at hospitals with and without on-site coronary artery bypass graft surgery (2007)
  • Author(s): Shiraishi J, Matoba S, et.al.
  • Journal Title: Circ J 71 Pages: 1208-12
  • NAID: 110006368843
• [Journal Article] Central role of calcium-dependent tyrosine kinase PYK2 in endothelial nitric oxide synthase-mediated angiogenic response and vascular function (2007)
  • Author(s): Matsui A, Matoba S, et.al.
  • Journal Title: Circulation 116 Pages: 1041-51
• [Journal Article] p53 shifts the balance of energy source in cardiac myocytes (2007)
  • Author(s): Kimata M, Matoba S, et.al.
  • Journal Title: Circulation 116
• [Journal Article] Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 11beta-hydoroxysteroid dehydrogenase 2 and prevents ventricular remodeling in post-infarct rat hearts (2007)
  • Author(s): Takeda M, Matoba S, et.al.
  • Journal Title: Hypertens Res 30 Pages: 427-437
• [Presentation] Hypoxia-Induced p53 Deteriorates Cardiac Energetics and Apoptotic Cell Death via TIGAR (2009)
  • Author(s): Masaki Kimata
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2009-03-22
• [Presentation] p53 and SCO2 (Synthesis of Cytochrome c Oxidase 2)Augments the Progression of Diabetic Cardiomyopathy (2009)
  • Author(s): Hideo Nakamura
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2009-03-22
• [Presentation] Hypoxia-Induced p53 Deteriorates Cardiac Energetics and Apoptotic Cell Death via TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) (2009)
  • Author(s): Kimata M, Matoba S, Iwai-kanai E, Nakamura H Hoshino A Nakaoka M, Hiraumi Y, Tatsumi T Matsubara H
  • Organizer: The 73nd Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
• [Presentation] p53 and SCO2 (Synthesis of Cytochrome c Oxidase 2) Augments the Progression of Diabetic Cardiomyopathy (2009)
  • Author(s): Nakamura H, Matoba S, Iwai-kanai E, Kimata M Hoshino A, Nakaoka M, Hiraumi Y, Tatsumi T Matsubara H
  • Organizer: The 73nd Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
• [Presentation] p53 is a new target to improve cardiac metabolism (2008)
  • Author(s): Masaki Kimata
  • Organizer: Basic Caridio Vascular Conference
  • Place of Presentation: 米国コロラド州
  • Year and Date: 2008-08-29
• [Presentation] p53 as a new target of cardiac metabolism (2008)
  • Author(s): 木股 正樹
  • Organizer: 日本循環器学会
  • Place of Presentation: 福岡市 福岡国際会議場
  • Year and Date: 2008-03-29
• [Presentation] p53 regulates cardiac metabolism as a new therapeutic target for heart failure (2008)
  • Author(s): 的場 聖明
  • Organizer: 日本循環器学会
  • Place of Presentation: 福岡市 福岡国際会議場
  • Year and Date: 2008-03-29
• [Presentation] p53 : New Therapeutic Target for Heart Failure (2008)
  • Author(s): Matoba S
  • Organizer: The 72nd Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka, Japan
• [Presentation] p53 is a new target to improve cardiac metabolism (2008)
  • Author(s): Kimata M, Matoba S, Nakamura H, Hoshino A, Nakaoka M, Hiraumi Y, Iwai-Kanai E, Tatsumi T, Matsubara H.
  • Organizer: Basic Cardiovascular Sciences Conference
  • Place of Presentation: Keystone, Colorado, U.S.A
• [Presentation] p53は嫌気的解糖を抑制し低酸素による心筋細胞のアポトーシスを増加させる (2008)
  • Author(s): 木股正樹、的場聖明、金井恵理、中村英夫 星野温、中岡幹彦、辰巳哲也、松原弘明
  • Organizer: 第17回日本アポトーシス研究会学術集会
  • Place of Presentation: 大津
• [Presentation] p53 shifts the balance of energy source in cardiac myocytes (2007)
  • Author(s): 木股 正樹
  • Organizer: アメリカ心臓学会
  • Place of Presentation: 米国 フロリダ州
  • Year and Date: 2007-11-04
• [Presentation] p53 regulates exercise capacity in mouse (2007)
  • Author(s): Matoba S, Kimata M, Tatsumi T, Matsubara H, Hwang PM.
  • Organizer: The 71st Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kobe, Japan
• [Presentation] p53 Shifts the Balance of Energy Source in Cardiac Myocytes (2007)
  • Author(s): Kimata M, Matoba S, Nakamura H, Tatsumi T, Matsubara H.
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orland Florida, U.S.A
• [Remarks] 平成21年3月21日再生医科学賞(臨床部門) 日本循環器学会
• [Remarks] 平成21年4月14日文部科学大臣表彰科学技術賞(開発部門) 文部科学省