心不全発症における心筋p300/GATA4経路活性化メカニズムの解明

2011 年度 研究成果報告書

• 研究課題/領域番号: 21590944
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 循環器内科学
• 研究機関: 静岡県立大学
• 研究代表者: 森本 達也 静岡県立大学, 薬学部, 教授 (50390779)
• 研究期間 (年度): 2009 – 2011
• キーワード: 心筋細胞肥大 / GATA4 / p300 / プロテオミクス / 転写因子

研究概要

我々は内因性ヒストンアセチル化酵素(HAT)活性を有するp300とGATA転写因子群の協力(p300/GATA経路)が心不全発症における遺伝子発現調節に極めて重要であることを示した。さらに、新規p300/GATA経路結合蛋白である、Cdk9, Ini1、RbAp48およびRbAp46が、p300/GATA経路と機能的複合体を形成し、心筋細胞肥大を制御することを見出した。

研究成果

• [雑誌論文] Cyclin-dependent kinase 9 forms a complex with GATA4 and is involved in the differentiation of mouse ES cells into cardiomyocytes (2011)
  • 著者名/発表者名: Kaichi S, Takaya T, Morimoto T, Sunagawa Y, Kawamura T, Ono K, Shimatsu A, Baba S, Heike T, Nakahata T, Hasegawa K
  • 雑誌名: J Cell Physiol 巻: 226(1) ページ: 248-54
• [雑誌論文] A natural p300-specific histone acetyltransferase inhibitor, curcumin, in addition to angiotensin converting enzyme inhibitor exerts beneficial effects on left ventricular systolic function after myocardial infarction in rats (2011)
  • 著者名/発表者名: Sunagawa Y, Morimoto T, Wada H, Takaya T, Katanasaka Y, Kawamura T, Yanagi S, Marui A, Sakata R, Shimatsu A, Kimura T, Kakeya H, Fujita M, Hasegawa K
  • 雑誌名: Circ J 巻: 75(9) ページ: 2151-9
• [雑誌論文] Innovative preparation of curcumin for Improved oral bioavailability (2011)
  • 著者名/発表者名: Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya K, Fujita M, Hasegawa K, Morimoto T
  • 雑誌名: Biol Pharm Bull 巻: 34(5) ページ: 660-5
• [雑誌論文] Cyclin-dependent kinsase-9 is a component of p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes (2010)
  • 著者名/発表者名: Sunagawa Y, Morimoto T, Takaya T, Wada H, Kawamura T, Fujita M, Shimatsu A, Kita T, Hasegawa K
  • 雑誌名: J Biol Chem 巻: 285(13) ページ: 9556-68
• [雑誌論文] Aldosterone Signaling Associates with p300/GATA4 Transcriptional Pathway during Hypertrophic Responses in Cardiomyocytes (2010)
  • 著者名/発表者名: Yoshida Y, Morimoto T, Takaya T, Kawamura T, Sunagawa Y, Wada H, Fujita M, Shimatsu A, Kita T, Hasegawa K
  • 雑誌名: Circ J 巻: 74(1) ページ: 156-62
• [雑誌論文] Left Ventricular Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Failing Rat Hearts (2010)
  • 著者名/発表者名: Takaya T, Wada H, Morimoto T, Sunagawa Y, Kawamura T, Takanabe-Mori R, Shimatsu A, Fujita Y, Sato Y, Fujita M, Kimura T, Sawamura T, Hasegawa K
  • 雑誌名: Circ J 巻: 74(4) ページ: 723-9
• [雑誌論文] Cell line-dependent differentiation of induced pluripotent stem cells into cardiomyocytes in mice (2010)
  • 著者名/発表者名: Kaichi S, Hasegawa K, Takaya T, Yokoo N, Mima T, Kawamura T, Morimoto T, Ono K, Baba S, Yamanaka S, Nakahata T, Heike T
  • 雑誌名: Cardiovasc Res 巻: 88(2) ページ: 314-23
• [雑誌論文] Excessive apoptosis as a downstream molecular event during the development of congenital heart diseases (2010)
  • 著者名/発表者名: Kaichi S, Hasegawa K, Morimoto T
  • 雑誌名: Circ J 巻: 74(11) ページ: 2297-8
• [雑誌論文] Hasegawa K Novel heart failure therapy targeting transcriptional pathway in cardiomyocytes by a natural compound, curcumin (2010)
  • 著者名/発表者名: Morimoto T, Sunagawa Y, Fujita M
  • 雑誌名: Circ J 巻: 74(6) ページ: 1059-66
• [雑誌論文] MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells (2009)
  • 著者名/発表者名: Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K
  • 雑誌名: Circ J 巻: 73(8) ページ: 1397-8
• [学会発表] Protein Arginine Methyltransferase 5 and Methylosome Protein 50 Suppressies Hypertrophic Responses in Cardiomyocytes by Inhibition of p300/GATA4 Pathway (2011)
  • 著者名/発表者名: Yasufumi Katanasaka, Yukiko Nakagawa, Yoichi Sunagawa, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: American Heart Association Scientific sessions 2011
  • 発表場所: Orland, USA
  • 年月日: 20111112-16
• [学会発表] SNF5/INI1 Inhibits Hypertrophic Responses by Suppressing p300/GATA4-dependent Pathways in Cardiomyocytes (2011)
  • 著者名/発表者名: Yoichi Sunagawa, Sugimoto Akihisa, Yukihiro Ishibashi, Yasufumi Katanasaka, Hiromichi Wada, Akira Shimatsu, Takeshi Kimura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: American Heart Association Scientific sessions 2011
  • 発表場所: Orland, USA
  • 年月日: 20111112-16
• [学会発表] Retinoblastoma Protein(Rb)-associated Protein 48 and 46 Form a Functional Complex With p300/GATA4 and Suppress Hypertrophic Responses in Cardiomyocytes (2011)
  • 著者名/発表者名: Yoichi Sunagawa, Yasufumi Katanasaka, Taishi Terada, Yuichi Watanabe, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: American Heart Association Scientific sessions 2011
  • 発表場所: Orland, USA
  • 年月日: 20111112-16
• [学会発表] A p300/GATA4 Transcriptional Pathway that Induces the Development of Heart Failure (2011)
  • 著者名/発表者名: Tatsuya Morimoto, Koji Hasegawa
  • 学会等名: The 7th Chica-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20111014-15
• [学会発表] Transducin beta-like protein 1 inhibits hypertrophic responses by recruiting HDAC3 to p300/GATA4 pathways (2011)
  • 著者名/発表者名: Masatoshi Namiki, Yasufumi Katanasaka, Yoichi Sunagawa, Hidetoshi Suzuki, Sho Hirota, Taishi Terada, Yukiko Nakagawa, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 7th Chica-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20111014-15
• [学会発表] Receptor for activated protein kinase C1 is a novel component of p300/GATA4 complex and suppresses hypertrophic responses in cardiomyocytes (2011)
  • 著者名/発表者名: Hidetoshi Suzuki, Yoichi Sunagawa, Yasufumi Katanasaka, Nobuko Okamura, Taishi Terada, Masatoshi Namiki, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 7th Chica-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20111014-15
• [学会発表] Protein arginine ethyltransferase 5 suppresses hypertrophic gene transcription in rat cardiomyocytes through the inhibition of p300/GATA4 pathway (2011)
  • 著者名/発表者名: Yasufumi Katanasaka, Yukiko Nakagawa, Yoichi Sunagawa, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 7th Chica-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20111014-15
• [学会発表] Retinoblastoma protein(Rb)-associated protein 48 and 46 are novel p300/GATA4-binding partners involved in hypertrophic responses in cardiomyocytes (2011)
  • 著者名/発表者名: Yoichi Sunagawa, Yasufumi Katanasaka, Taishi Terada, Yuichi Watanabe, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: American Heart Association BCVS2011
  • 発表場所: New Orleans, USA
  • 年月日: 20110718-21
• [学会発表] Protein arginine metyltransferase 5 and methylosome protein 50 are novel component of p300/GATA4 complex involved in hypertrophic responses in cardiac myocytes (2011)
  • 著者名/発表者名: Yasufumi Katanasaka, Yukiko Nakagawa, Yoichi Sunagawa, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: American Heart Association BCVS2011
  • 発表場所: New Orleans, USA
  • 年月日: 20110718-21
• [学会発表] Retinoblastoma Protein(Rb)-associated Protein 48 and 46 are Novel Components of p300/GATA4 Complex Required for Hypertrophic Responses in Cardiomyocytes (2011)
  • 著者名/発表者名: Yoichi Sunagawa, Yasufumi Katanasaka, Taishi Terada, Yuichi Watanabe, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 14th Annual International Tronto Heart Summit
  • 発表場所: Tronto, Canada
  • 年月日: 20110609-11
• [学会発表] Protein arginine metyltransferase 5 and methylosome protein 50 are novel component of p300/GATA4 complex involved in hypertrophic responses in cardiac myocytes (2011)
  • 著者名/発表者名: Yasufumi Katanasaka, Yukiko Nakagawa, Yoichi Sunagawa, Masatoshi Fujita, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 14th Annual International Tronto Heart Summit
  • 発表場所: Tronto, Canada
  • 年月日: 20110609-11
• [学会発表] Heart f ailure therapy that targets nuclear signaling pathway in cardiomyocytes. from bench to bedside (2009)
  • 著者名/発表者名: Tatsuya MorimotoKoji Hasegawa
  • 学会等名: The 25th Annual Meeting of ISHR Japanese Section, Scientific Program
  • 発表場所: Sapporo, Japan
  • 年月日: 20091204-05
• [学会発表] A novel component of p300/GATA4 complex, Cyclin-dependent kinsase-9, is required for hypertrophic responses in cardiomyocytes (2009)
  • 著者名/発表者名: Yoichi Sunagawa, Tatsuya Morimoto, Masatoshi FujitaKoji Hasegawa
  • 学会等名: The 25th Annual Meeting of ISHR Japanese Section Scientific Program
  • 発表場所: Sapporo, Japan
  • 年月日: 20091204-05
• [学会発表] A natural p300-specific histone acetyltransferase inhibitor, curcumin, exerts synergistic effects with ACE inhibitor during systolic function restoration after myocardial infarction in rats (2009)
  • 著者名/発表者名: Yoichi Sunagawa, Tatsuya Morimoto, Hiromichi Wada, Tomohide Takaya, Teruhisa Kawamura, Shigeki Yanagi, Akira Marui, Tadashi Ikeda, Ryuzo Sakata, Akira Shimatsu, Takeshi Kimura, Masatoshi FujitaKoji Hasegawa
  • 学会等名: The 82th American Heart Association Annual Scientific Sessions
  • 発表場所: Orlando, USA
  • 年月日: 20091115-19
• [学会発表] Novel drug-delivery system of oral curcumin that prevents the deterioration of systolic function after myocardial infarction in rats (2009)
  • 著者名/発表者名: Yoichi Sunagawa, Hiroyuki Fukuda, Hiromichi Wada, Tomohide Takaya, Akira Marui, Kazuhide Uemura, Akira Shimatsu, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
  • 学会等名: The 82th American Heart Association Annual Scientific Sessions
  • 発表場所: Orlando, USA
  • 年月日: 20091115-19
• [学会発表] Curcumin Prevents the Development of Hypertension-induced Left Ventricular Hypertrophy in Rats (2009)
  • 著者名/発表者名: Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Kazuhide Uemura, Akira Shimatsu, Takeshi Kimura, Masatoshi FujitaKoji Hasegawa
  • 学会等名: The 82th American Heart Association Annual Scientific Sessions
  • 発表場所: Orlando, USA
  • 年月日: 20091115-19
• [学会発表] Curcumin exerts synergistic effects with ACE inhibitor during LV systolic function restoration after rat myocardial infarction (2009)
  • 著者名/発表者名: Yoichi Sunagawa, Tatsuya Morimoto, Tomohide Takaya, Masatoshi Fujita, Takeshi KimuraKoji Hasegawa
  • 学会等名: The 5th China-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20091011-12
• [学会発表] Cdk9 kinase activity is required for p300 phosphorylation and regulate transcriptional pathway during hypertrophic responses in cardiomyocytes (2009)
  • 著者名/発表者名: Taishi Terada, Tatsuya Morimoto, Yoichi Sunagawa, Masatoshi Fujita, Takeshi KimuraKoji Hasegawa
  • 学会等名: The 5th China-Japan Cardiovascular Forum
  • 発表場所: Beijing, China
  • 年月日: 20091011-12
• [学会発表] A natural p300-specific histone acetyltransferase inhibitor, Curcumin, can prevent the development of heart failure in addition to ACE inhibitor after myocardial infarction in rats (2009)
  • 著者名/発表者名: Tatsuya Morimoto, Masatoshi Fujita, Yoichi Sunagawa, Hiromichi Wada, Tomohide Takaya, Shigeki Yanagi, Akira Marui, Tadashi Ikeda, Akira ShimatsuKoji Hasegawa
  • 学会等名: European Society of Cardiology Congress
  • 発表場所: Barcelona, Spain
  • 年月日: 20090829-0902
• [学会発表] A Natural p300-specific HAT Inhibitor, Curcumin, Possesses Beneficial Effects in Addition to ACE Inhibitor after Rat Myocardial Infarction (2009)
  • 著者名/発表者名: Tatsuya Morimoto, Yoichi Sunagawa, Hiromichi Wada, Tomohide Takaya, Shigeki Yanagi, Akihiro Sugimoto, Masaki Tsukashita, Akira Marui, Tadashi Ikeda, Masatoshi Fujita, Akira Shimatsu, Toru KitaKoji Hasegawa
  • 学会等名: 17th Asian Pacific Congress of Cardiology
  • 発表場所: Kyoto, Japan
  • 年月日: 20090520-23
• [備考]
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/～byoutai/