Purification and analysis of a transoription factor, GATA4 complex from adult mouse heart during developing heart failure
Project/Area Number |
19590842
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
Principal Investigator |
MORIMOTO Tatsuya Department of Clinical Research, National Hospital Organization Kyoto Medical Center, 展開医療研究部, 主任研究員 (50390779)
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Co-Investigator(Kenkyū-buntansha) |
SHIOI Tetsuo 京都大学, 医学研究科・循環器内科学, 講師 (50360095)
|
Project Period (FY) |
2007 – 2008
|
Project Status |
Completed (Fiscal Year 2008)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | プロテオミクス / 心筋細胞肥大 / 転写因子 / p300 / GATA4 / Cdk9 / トランスジェニックマウス / GATA-4 |
Research Abstract |
(1)新規p300/GATA結合蛋白の同定 GATA4複合体を構成する蛋白を網羅的に解析し、73個の結合蛋白を同定した。この結合蛋白の中には、転写に重要な役割を果たしている蛋白が含まれていた。転写の伸長反応の促進に関与するP-TEFb (positive transcription elongation factor・b)、ATP 依存的にクロマチン構造を変化させ転写を制御するクロマチンリモデリング因子であるSWI/SNF複合体、クロマチン構築因子Chromatin Assembly Factor-1 (CAF-1)などが含まれていた。 (2)P-TEFbによるp300/GATA経路活性化のメカニズムの解明 73個の結合タンパクの中で、我々はP-TEFbに着目した。P-TEFbはCdk9とCyclin T1のタイマーからなり、RNA polymeraseII を制御することが知られている。GST pull-down アッセイにより、Cdk9はGATA4と、さらにはp300と直接結合した。培養心筋細胞を用いた実験で、Cdk9のキナーゼ阻害薬であるDRBは、フェニレフリン刺激による肥大反応を抑制した。DRBは、フェニレフリン刺激によるp300のリン酸化およびGATA4のアセチル化の増加を抑制した。また、フェニレフリン刺激によってGATA4とCdk9の結合が増加し、Cdk9はGATA4によって肥大反応遺伝子であるANFプロモーター上にリクルートされる事を見出した。さらに、フェニレフリン刺激によるAN遺伝子のプロモーター活性をDRBが抑制する事がわかった。このことより、肥大刺激によるp300/GATA経路の活性にCdk9のキナーゼ活性が必要であることが示された。
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Report
(3 results)
Research Products
(89 results)
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[Journal Article] Statins activate GATA-6 and induce differentiatedvascular smooth muscle cells2008
Author(s)
Wada H, Abe M, Ono K, Morimoto T, Kawamura T, Takaya T, Satoh N, Fujita M, Kita T, Shimatsu A, Hasegawa K
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Journal Title
Biochem Biophys Res Commun. 374(4)
Pages: 731-6
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Peer Reviewed
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[Journal Article] Knowledge and interest regarding smoking-related health risks in smokers and non-smokers. Self-rating depression scale score is a strong independent predictor of smoking cessation outcomes2008
Author(s)
Wada H, Hasegawa K, Terashima S, Satoh N, Inoue M, lida Y, Yamakage H, Kitaoka S, Morimoto T. Fujita M, Shimatsu A, Takahashi Y
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Journal Title
Smoking Control Science 4
Pages: 4-8
Related Report
Peer Reviewed
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[Journal Article] The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats2008
Author(s)
Morimoto T, Sunagawa Y, Kawamura T, Takaya T, Wada H, Nagasawa A, Komeda M, Fujita M, Shimatsu A, Kita T, Hasegawa K
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Journal Title
J Clin Invest 118
Pages: 868-78
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Peer Reviewed
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[Journal Article] Statins activate GATA-6 and induce differentiated vascular smooth muscle cells2008
Author(s)
Wada H, Abe M, Ono K, Morimoto T, Kawamura T, Takaya T, Satoh N, Fujita M, Kita T, Shimatsu A, Hasegawa K
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Journal Title
Biochem Biophys Res Commun 374
Pages: 731-6
Related Report
Peer Reviewed
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[Journal Article] Knowledge and interest regarding smoking-related health risks in smokers and nonsmokers. Self-rating depression scale score is a strong independent predictor of smoking cessation outcomes2008
Author(s)
Wada H, Hasegawa K, Terashima S, Satoh N, Inoue M, Iida Y, Yamakage H, Kitaoka S, Morimoto T, Fujita M, Shimatsu A, Takahashi Y.
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Journal Title
Smoking Control Science 4
Pages: 4-8
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Peer Reviewed
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[Journal Article] 心筋細胞核をターゲットとした新しい心不全治療の可能性2007
Author(s)
森本達也, 砂川陽一, 川村晃久, 高谷智英, 和田啓道, 宮本昌一, 長澤淳, 米田正始, 藤田正俊, 島津章, 北徹, 長谷川浩二
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Journal Title
適応医学誌 Vol.1l.No.2
Pages: 19-26
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[Presentation] Cell Line-dependent Differentiation of Mouse Induced-pluripotent Stem Cells into Cardiomyocytes2009
Author(s)
Shinji Kaichi, Tomohide Takaya, Tatsuya Morimoto, Yoichi Sunagawa, Teruhisa Kawamura, Koh Ono, Toru Kita, Kyoko Hidaka, Takayuki Morisaki, Shiro Baba, Toshio Heike, Tatsutoshi Nakahata, Koji Hasegawa
Organizer
臨床心血管再生研究会
Place of Presentation
京都
Year and Date
2009-03-04
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[Presentation] Self-rating Depression Scale score is a Strong Independent Predictor of Smoking Cessation Outcomes2009
Author(s)
Hiromichi Wada, Koji Hasegawa, Sachiko Terashima, Noriko Satoh, Misuzu Inoue, Yuko Iida, Hajime Yamakage, Shuji Kitaoka, Tatsuya Morimoto, Masatoshi Fujita, Akira Shimatsu, Yuko Takahashi
Organizer
第73回日本循環器学会
Place of Presentation
大阪
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[Presentation] Synergistic Effects of G-CSF and Erythropoietin on Left Ventricular Systolic Function in Heart Failure after Rat Myocardial Infarction2009
Author(s)
Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromicht Wada, Tomoaki Kuwaki, Shigeki Yanagi, Akihiro Sugimoto, Masaki Tsukashita, Akira Marui, Tadashi Ikeda, Akira Shimatsu, Masatoshi Fujita, Toru Kita, Koji Hasegawa
Organizer
第73回日本循環器学会
Place of Presentation
大阪
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[Presentation] Cell Line-dependent Differentiation of Mouse Induced-pluripotent Stem Cells into Cardiomyocytes2009
Author(s)
Shinji Kaichi, Tomohide Takaya, Tatsuya Morimoto, Yoichi Sunagawa, Teruhisa Kawamura, Koh Ono, Toru Kita, Kyoko Hidaka, Takayuki Morisaki, Shiro Baba, Toshio Heike, Tatsutoshi Nakahata, Koji Hasegawa
Organizer
第73回日本循環器学会
Place of Presentation
大阪
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[Presentation] p300/GATA4複合体の新規構成因子であるCDK9はES細胞から心筋への初期分化に重要な役割を果たす2008
Author(s)
鶏内伸二, 高谷智英, 森本達也, 砂川陽一, 川村晃久, 尾野亘, 北徹, 日高京子, 森崎隆幸, 馬場志郎, 平家俊男, 中畑龍俊, 長谷川浩二
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第8回心血管再生先端治療フォーラム
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東京
Year and Date
2008-07-05
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[Presentation] 天然成分クルクミンを用いた新規心不全治療2008
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森本達也, 砂川陽一, 川村晃久, 高谷智英, 和田啓道, 米田正始, 藤田正俊, 島津章, 北徹, 長谷川浩二
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第2回京都循環器フロンティアフォーラム
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京都
Year and Date
2008-06-17
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[Presentation] Curcumin, a Natural p300-specific Histone Acetyltransferase Inhibitor, Prevents the Development of Heart Failure in Rats2008
Author(s)
Tatsuya Morimoto, Yoichi Sunagawa, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Shoichi Miyamoto, Atsushi Nagasawa, Shigeki Yanagi, Ryota Sugimoto, Akira Marui, Masashi Komeda, Masatoshi Fujita, Akira Shimatsu, Toru Kita, Koji Hasegawa
Organizer
Keystone Symposia
Place of Presentation
Colorado, USA
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[Presentation] Curcumin, a Natural p300-specific Histone Acetyltransferase Inhibitor, Prevents the Development of Cardiac Hypertrophy in Rats2008
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Tatsuya Morimoto, Masatoshi Fujita, Yoichi Sunagawa, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Akira Shimatsu, Tom Kita, Koji Hasegawa
Organizer
European Society of Cardiology Congress
Place of Presentation
Munich, Germany
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[Presentation] Granulocyte-colony stimulating factor and erythropoietin synergistically improve left ventricular systolic function in heart failure after myocardial infarction in rats2008
Author(s)
Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Tomoaki Kuwaki, Shigeki Yanagi, Akihiro Sugimoto, Masaki Tsukashita, Akira Mami, Tadashi Ikeda, Akira Shimatsu, Masatoshi Fujita, Tom Kita, Koji Hasegawa
Organizer
The 81^<th> American Heart Association Annual Scientific Sessions
Place of Presentation
New Orleans, USA
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[Presentation] Cardiac-specific transcription in ES cells by Cdk92008
Author(s)
S Kaichi, T Takaya, T Morimoto, Y Sunagawa, T Kawamura, K Ono, T Kita, T Heike, T Nakahata, K Hasegawa
Organizer
The 25th Annual Meeting of ISHR Japanese Section
Place of Presentation
Yokohama, Japan
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[Presentation] Cyclin-dependent Kinase-9, As A Novel Component Of p300/GATA4 Complex, Is Involved In The Differentiation Of Mouse ES Cells Into Cardiac Myocytes2008
Author(s)
S Kaichi, T Takaya, T Morimoto. Y Sunagawa, T Kawamura, K Ono, T Kita, T Heike, T Nakahata, K Hasegawa
Organizer
BIT Life Sciences' 1st Annual World Congress of Regenerative Medicine & Stem Cell
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Guangzhou, China
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[Presentation] Cyclin-dependent Kinase-9, As A Novel Component Of p300/GATA4 Complex, Is Involved In The Differentiation Of Mouse ES Cells Into Cardiac Myocytes2008
Author(s)
S Kaichi, T Takaya, T Morimoto. Y Sunagawa, T Kawamura, K Ono, T Kita, T Heike, T Nakahata, K Hasegawa
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第72回日本循環器学会
Place of Presentation
博多、福岡
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[Presentation] MicroRNA-1の過剰発現はマウスES細胞の心筋分化を抑制する2008
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高谷智英, 川村晃久, 尾野亘, 高鍋利依子, 鵜内伸二, 馬場志郎, 平家俊男, 中畑龍俊, 森本達也, 北徹, 島津章, 長谷川浩二
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第45回日本臨床分子医学会
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神戸
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[Presentation] G-CSF/エリスロポエチン併用療法はラット心筋梗塞後の左室機能低下を改善する2008
Author(s)
森永智子, 森本達也, 砂川陽一, 高谷智英, 桑木知朗, 柳茂樹, 杉本亮大, 塚下将樹, 丸井晃, 池田義, 川村晃久, 和田啓道, 島津章, 長谷川浩二, 藤田正俊
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第12回 Molecular Cardiovascular Conference
Place of Presentation
キロロ
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[Presentation] Synergistic Effects of Granulocyte-colony stimulating factor and Erythropoietin on Left Ventricular Systolic Function in Rat Myocardial Infarction2008
Author(s)
Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Tomoaki Kuwaki, Shigeki Yanagi, Akihiro Sugimoto, Masaki Tsukashita, Akira Marui, Tadashi Ikeda, Akira Shimatsu, Masatoshi Fujita, Tom Kita, Koji Hasegawa
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第12回日本心不全学会学術集会
Place of Presentation
横浜
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[Presentation] Curcumin, a Natural p300-specific Histone Acetyltransferase Inhibitor, Prevents the Development of Heart Failure in Rats2007
Author(s)
Tatsuya Morimoto, Yoichi Sunagawa, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Shoichi Miyamoto, Atsushi Nagasawa, Masashi Komeda, Masatoshi Fujita, Akira Shimatsu, Toru Kita, Koji Hasegawa
Organizer
The 80^<th> American Heart Association Annual Scientific Sessions
Place of Presentation
Orlando, USA
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[Presentation] A Natural p300-specific Histone Acetyltransferase Inhibitor, curcumin, Prevents the Development Heart Failure in rats2007
Author(s)
Tatsuya Morimoto, Yoichi Sunagawa, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Shoichi Miyamoto, Atsushi Nagasawa, Masashi Komeda, 2Masatoshi Fujita, Akira Shimatsu, Toru Kita, Koji
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The 14^<th> International Congress on Cardiovascular Pharmacotherapy
Place of Presentation
Antalya Turkey
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[Presentation] 心筋細胞核内アセチル化抑制による新しい心不全治療薬の検討2007
Author(s)
砂川陽一, 森本達也, 高谷智英, 和田啓道, 宮本昌一, 川村晃久, 長澤淳, 米田正始, 藤田正俊, 島津章, 北徹, 長谷川浩二
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第44回日本臨床分子医学会
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和歌山
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[Presentation] A Natural p300-specific Histone Acetyltransferase Inhibitor, Crucumin, Prevents the Development of Heart Failure in vivo2007
Author(s)
Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Shoichi Miyamoto, Hiromichi Wada, Akira Shimatsu, Masatoshi Fujita, Toru Kita, Koji Hasegawa
Organizer
第11回日本心不全学会学術集会
Place of Presentation
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[Presentation] 天然物ウコン成分クルクミンによる心筋細胞核内アセチル化抑制を介した心不全治療2007
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森本達也, 砂川陽一, 川村晃久, 高谷智英, 和田啓道, 宮本昌一, 長澤淳, 米田正始, 島津章, 藤田正俊, 北徹, 長谷川浩二
Organizer
第11回Molecular Cardiovascular Conference
Place of Presentation
キロロ
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