Research for heart failure by regulating mitochondrial energy metabolism with p53

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590938
• 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 京都府立医科大学, 医学研究科, 助教 (10305576)
• Co-Investigator(Kenkyū-buntansha): KANAI Eri 明治国際医療大学, 医学教育研究センター, 教授 (20372584)
• Project Period (FY): 2009 – 2011
• Keywords: p53 / 心不全 / ミトコンドリア / エネルギー代謝

Research Abstract

Ischemia or hyperglycemia induced p53, SCO2(Synthesis of cytochrome c oxidase 2) and TIGAR(TP53-induced glycolysis and apoptosis regulator) in the heart. We demonstrated diabetic condition induced SCO2, which promoted cardiac lipotoxicity(Circ Heart Fail. 2012). Ischemia induced p53 and TIGAR, which inhibited glycolysis(Am J Physiol Heart Circ Physiol. 2010) and mitophagy in the myocardium(J Mol Cell Cardiol. 2012). We also found that p53/TIGAR-mediated inhibition of myocyte mitophagy was responsible for ventricular remodeling after myocardial infarction.(J Mol Cell Cardiol 2012). SCO2 heterozygote mice were protective against diabetes induced cardiomyopathy. These data indicated that regulating energy metabolism will be a novel therapeutics for heart failure.

Research Products

• [Journal Article] p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia (2012)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Nakamura H, Kimata M, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Ikeda K, Ueyama T, Okigaki M, Matsubara H
  • Journal Title: J Mol Cell Cardiol Volume: 52 Pages: 175-184
• [Journal Article] p53 promotes cardiac dysfunction in diabetic mellitus due to excessive mitochondrial respiration-mediated ROS generation and lipid accumulation (2012)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Ikeda K, Okigaki M, Tanaka H, Takamatsu T, Matsubara H
  • Journal Title: Circ Heart Fail Volume: 5 Pages: 106-115
• [Journal Article] 15-deoxy-δprostaglandin j(2) reduces the formation of atherosclerotic lesions in apolipoprotein e knockout mice (2011)
  • Author(s): Seno T, Hamaguchi M, Ashihara E, Kohno M, Ishino H, Yamamoto A, Kadoya M, Nakamura K, Murakami K, Matoba S, Maekawa T, Kawahito Y
  • Journal Title: PLoS One Volume: 6(10) Pages: e25541
• [Journal Article] p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress (2010)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Okigaki M, Ikeda K, Tatsumi T, Matsubara H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 299 Pages: 1908-1916
• [Presentation] p53 mediated inactivation of Bnip3 reduces mitophagy to aggravate cardiac damage after ischemic injury (2012)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Matsubara H
  • Organizer: 第75回日本循環器病学会
  • Place of Presentation: 横浜
  • Year and Date: 20120000
• [Presentation] p53 Promotes Cardiac Dysfunction in Diabetes Mellitus by Excessive Mitochondrial Respiration and Fat/CD36 Upregulation (2012)
  • Author(s): Matoba S
  • Organizer: 第76回日本循環器病学会
  • Place of Presentation: 福岡
  • Year and Date: 20120000
• [Presentation] Granulocyte colony-stimulating Factor(G-CSF) Protects Cardiac Myocytes Against Doxorubicin Induced Injury Via the Stabilization of MDM2 (2012)
  • Author(s): Mita Y, Iwai-Kanai E, Matoba S, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Adachi S, Matsubara H
  • Organizer: 第76回日本循環器病学会
  • Place of Presentation: 福岡
  • Year and Date: 20120000
• [Presentation] Curcumin Protect Mice Heart against Doxorubicin Induced Cardiomyopathy thorough the Induction of Autophagy (2012)
  • Author(s): Nakaoka M, Iwai-Kanai E, Matoba S, Mita Y, Kimata M, Nakamura H, Hoshino A, Katamura M, Okawa Y, Ariyoshi M, Adachi S, Matsubara H
  • Organizer: 第76回日本循環器病学会
  • Place of Presentation: 福岡
  • Year and Date: 20120000
• [Presentation] p53 promotes cardiac dysfunction in diabetes mellitus by excessive mitochondrial respiration and Fat/CD36 upregulation (2011)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Ariyoshi M, Ikeda K, Okigaki M, Matsubara H
  • Organizer: 米国心臓病学術会議
  • Place of Presentation: Orlando, USA
  • Year and Date: 20110000
• [Presentation] p53-Tigar Axis Attenuates Mitophagy Tt Exacerbate Cardiac Damage After Ischemia (2011)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Orlando, USA
  • Year and Date: 20110000
• [Presentation] p53 promotes cardiac aging through the inhibition of parkin mediated mitochondrial quality control (2011)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Orlando, USA
  • Year and Date: 20110000
• [Presentation] p53 activation provokes mitochondrial compromise and cardiac aging (2011)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Matsubara H
  • Organizer: NHLBI Mitochondrial biology symposium Orlando
  • Place of Presentation: USA
  • Year and Date: 20110000
• [Presentation] G-CSFによる心筋保護効果と抗癌作用への影響 (2011)
  • Author(s): 三田雄一郎, 的場聖明, 星野温, 中岡幹彦, 片村真紀, 大川善文, 有吉真, 足立壮一, 松原弘明, 金井恵理
  • Organizer: 第20回cell death学会
  • Place of Presentation: 東京
  • Year and Date: 20110000
• [Presentation] クルクミンはドキソルビシンによる心筋障害に対し保護的に働く (2011)
  • Author(s): 片村真紀, 的場聖明, 星野温, 中岡幹彦, 大川善文, 有吉真, 三田雄一郎, 足立壮一, 松原弘明, 金井恵理
  • Organizer: 第20回cell death学会
  • Place of Presentation: 東京
  • Year and Date: 20110000
• [Presentation] p53発現抑制によるオートファジー亢進を介した心筋保護効果 (2011)
  • Author(s): 的場聖明, 星野温, 金井恵理, 中村英夫, 中岡幹彦, 片村真紀, 大川善文, 有吉真, 三田雄一郎, 松原弘明
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 20110000
• [Presentation] p53-mediated acceleration of mitochondrial oxygen consumption promotes lipotoxicity via SCO2 in diabetic mice (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Tatsumi T, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Chicago
  • Year and Date: 20101113-17
• [Presentation] p53-mediated decrease in ROS signal reduces mitophagy via inactivation of Bnip3 to aggravate cardiac damage after ischemic injury (2010)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Nakaoka M, Katamura M, Okawa Y, Mita Y, Tatsumi T, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-17
• [Presentation] 糖尿病性心筋障害において、p53の活性化は脂肪毒性を亢進する (2010)
  • Author(s): 中村英夫, 的場聖明, 金井恵理, 木股正樹, 星野温, 中岡幹彦, 片村真紀, 大川善文, 三田雄一郎, 松原弘明
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20101000
• [Presentation] 心筋虚血においてp53はミトファジーを抑制し心筋障害を増大する (2010)
  • Author(s): 星野温, 的場聖明, 金井恵理, 中岡幹彦, 木股正樹, 中村英夫, 片村真紀, 大川義文, 三田雄一郎, 松原弘明
  • Organizer: 第19回日本cell death学会
  • Place of Presentation: 名古屋
  • Year and Date: 20100800
• [Presentation] p53 promotes heart failure in diabetic cardiomyopathy (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Tatsumi T, Matsubara H
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] p53/TIGAR System Inhibits Glucose Metabolism and Augments Myocyte Apoptosis in Ischemic heart (2010)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Tatsumi T, Matsubara H
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] p53 inhibits autophagy and accelerates apoptotic cell death through mitochondrial redox signal in ischemic myocardium (2010)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Nakaoka M, Katamura M, Tatsumi T, Matsubara H
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] p53 promotes heart failure in diabetic mice (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Matsubara H
  • Organizer: The 11th US-Japan-Asia Dialogue
  • Place of Presentation: Tokyo
  • Year and Date: 2010-08-21
• [Presentation] p53 accelerates cardiac damage in diabetes (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Matsubara H
  • Organizer: International Society of Heart Research
  • Place of Presentation: Kyoto
  • Year and Date: 2010-05-14
• [Presentation] Differential Roles of Akt and Extracellular Signal-Regulated Kinase Signaling Pathways on Autophagy During Alpha1-Adrenergic Agonist-Mediated Cardioprotection (2009)
  • Author(s): Nakaoka M, Iwai-Kanai E, Matoba S, Kimata M, Nakamura H, Hoshino A, Katamura M, Hiraumi Y, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Orlando, USA
  • Year and Date: 20091114-18
• [Presentation] 交感神経の亢進による心筋オートファジーの誘導 (2009)
  • Author(s): 中岡幹彦, 金井恵理, 的場聖明, 木股正樹, 中村英夫, 星野温, 片村真紀, 松原弘明
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津
  • Year and Date: 20091000
• [Presentation] p53による解糖系調節とアポトーシス制御 (2009)
  • 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, 平海良美, 片村真紀, 辰巳哲也, 松原弘明
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津
  • Year and Date: 20091000
• [Presentation] p53発現抑制におけるオートファジーを介した虚血心筋保護効果 (2009)
  • Author(s): 星野温, 的場聖明, 金井恵理, 中岡幹彦, 木股正樹, 中村英夫, 片村真紀, 松原弘明
  • Organizer: 第18回日本cell death学会
  • Place of Presentation: 長崎
  • Year and Date: 20090800
• [Presentation] 交感神経刺激による心筋アポトーシス、オートファジーの制御 (2009)
  • Author(s): 中岡幹彦, 金井恵理, 的場聖明, 木股正樹, 中村英夫, 星野温, 片村真紀, 松原弘明
  • Organizer: 第18回日本cell death学会
  • Place of Presentation: 長崎
  • Year and Date: 20090800
• [Presentation] p53 and SCO2(Synthesis of Cytochrome c Oxidase 2) Augment the Progression of Diabetic Cardiomyopathy (2009)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Tatsumi T, Matsubara H
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 20090300
• [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, Katamura M, Tatsumi T, Matsubara H
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 20090300
• [Presentation] p53 Promotes Heart Failure With Lipid Accumulation in Diabetes (2009)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Tatsumi T, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Orlando, USA
  • Year and Date: 2009-11-17
• [Remarks] ホームページ等にて研究内容を説明
  • URL: http://www.f.kpu-m.ac.jp/k/med2/group/cardio/kenkyu-01.html