Aldosterone Signaling Associates With p300/GATA4 Transcriptional Pathway During the Hypertrophic Response of Cardiomyocytes
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概要
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Background: Aldosterone exerts its effect by binding to specific mineralocorticoid receptors (MRs). Spironolactone blocks the aldosterone system, which ameliorates heart failure in humans, but the precise molecular mechanisms of MR blockade are unclear. Methods and Results: Neonatal rat cardiomyocytes were stimulated with phenylephrine (PE), aldosterone, and/or spironolactone. The association of the MR with p300, a transcriptional coactivator of GATA4 required for hypertrophic responses, was examined. MR and p300 synergistically activated GATA4-dependent atrial natriuretic factor (ANF) promoter activities. The stimulation of cardiomyocytes with PE induced translocation of the MRs into the nuclei and markedly increased the association of MRs with p300. Compatible with the synergistic activation by the MR and p300, aldosterone further augmented the PE-induced increase in cell size and induction of ANF gene transcription. Blockade of MR activation by spironolactone inhibited the PE-induced nuclear translocation of MRs and hypertrophic responses. Conclusions: For the first time it has been demonstrated that the aldosterone/MR system associates with the p300/GATA4 transcriptional pathway during the hypertrophic response of cardiomyocytes, and may provide a mechanism of the beneficial effects of aldosterone-blocking agents in heart failure therapy in humans.
- 社団法人 日本循環器学会の論文
- 2009-12-20
著者
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Hasegawa Koji
Division of Translational Research, National Hospital Organization, Kyoto Medical Center
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北 徹
Department Of Geriatric Medicine Osaka University Graduate School Of Medicine
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北 徹
京都大学老年科
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KITA Toru
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
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KATSUYA Tomohiro
Osaka University
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Kudoh T
Department Of Cardiovascular Respiratory And Metabolic Medicine Graduate School Of Medicine Kagoshim
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Kudoh Takashi
京都大学 医研究 循環病態
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Kudoh Takashi
Department Of Nuclear Medicine Kyoto University Faculty Of Medicine
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Kita Toru
Department Of Cardiovascular Medicine Kobe City Medical Center General Hospital
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Kita Toru
Department Of Cardiovascular Medicine Kyoto University
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Miyamoto Tadashi
Department Of Cardiology Hyogo Prefectural Amagasaki Hospital
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Morimoto Takeshi
神戸市立医療センター中央市民病院 循環器内科
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Takaya Tomohide
Division Of Translational Research Kyoto Medical Center
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Takaya Tomohide
国立病院機構京都医療センター 展開医療研究部
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Kobayashi Takashi
Department Of Cardiology Kobe City Medical Center General Hospital
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Morimoto Tatsuya
Center For Medical Education Kyoto University Graduate School Of Medicine
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Shimatsu Akira
Division Of Clinical Research Institute Kyoto Medical Center
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Shimatsu Akira
国立病院機構京都医療センター 展開医療研究部
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SHIMATSU AKIRA
Clinical Research Institute, Kyoto National Hospital
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Kita Toru
Department Of Geriatric Medicine Graduate School Of Medicine Kyoto University
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Katsuya Tomohiro
東北大学 臨床薬学
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Fujita Masatoshi
国立病院機構京都医療センター 展開医療研究部
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Fujita M
Human Health Sciences Graduate School Of Medicine Kyoto University
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Fujita M
School Of Health Sciences Faculty Of Medicine Institute For Frontier Medical Sciences Kyoto Universi
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Kita Toru
Department Of Cardiology Kobe City Medical Center General Hospital
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Kurita Takashi
Division Of Cardiology Department Of Internal Medicine National Cardiovascular Center
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Morimoto Tatsuya
京都大学 医研究 循病態
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Morimoto Tatsuya
Division Of Translational Research Kyoto Medical Center
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Kubo Takashi
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Kotake Takeshi
国立医薬品食品衛生研究所
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YOSHIDA Yoshinori
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
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TAKAYA Tomohide
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
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KAWAMURA Teruhisa
Division of Translational Research, Kyoto Medical Center National Hospital Organization
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SUNAGAWA Yoichi
Division of Translational Research, Kyoto Medical Center National Hospital Organization
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WADA Hiromichi
Division of Translational Research, Kyoto Medical Center National Hospital Organization
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FUJITA Masatoshi
Human Health Sciences, Graduate School of Medicine, Kyoto University
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Hidaka Kyoko
京都大学 医学部小児科
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Wada Hiromichi
Division Of Translational Research Kyoto Medical Center
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Wada Hiromichi
国立病院機構京都医療センター 展開医療研究部
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Wada Hiromichi
Division Of Engineering Graduate School Of Kansai Univ.
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Kasai Takatoshi
Department Of Cardiology Juntendo University
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Shimatsu Akira
Clinical Research Institute Kyoto Medical Center National Hospital Organization
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KIMURA Tokihisa
Furukawa City Hospital
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Wada Hiromichi
Division Of Translational Research Kyoto Medical Center National Hospital Organization
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Wada Hiromichi
Department Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine
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Kizu Takashi
大阪大学 医学系研究科内分泌・代謝内科
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Morimoto Tatsuya
Division Of Translational Research Kyoto Medical Center National Hospital Organization
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Shimatsu Akira
国立病院機構京都医療センター 代謝臨床研究センター内分泌研究部
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Shimatsu Akira
Clinical Research Center For Endocrine And Metabolic Disease Kyoto Medical Center
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Kurita Takashi
The NATIVE
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Takaya Tomohide
Division Of Translational Research Kyoto Medical Center National Hospital Organization
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Miyamoto Tadashi
兵庫県立尼崎病院 循環器内科
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Tanaga Kosei
千葉県循環器病センター 循環器科
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Shimatsu Akira
Division Of Preventive Medicine Clinical Research Institute National Hospital Organization Kyoto Med
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Morita Toshihiro
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Miyamoto Tadashi
Center For Medical Education Kyoto University Graduate School Of Medicine
-
Hasegawa Koji
Division Of Translational Research Kyoto Medical Center National Hospital Organization
-
Kobayashi Takashi
Department Of Cardiology National Cardiovascular Center
-
Morishita Tetsuji
福井大学医学部附属病院 循環器内科
-
Kuwahara Taishi
Cardiovascular Center Yokosuka Kyosai Hospital
-
FUJITA MASATOSHI
Otowa Hospital
-
Kudou T
Kyoto Univ.
-
Hasegawa Koji
Department Of Cardiovascular Medicine Graduate School Of Medicine Kyoto University
-
Kimura Takeshi
Department Of Cardiology Kobe City Medical Center General Hospital
-
Tamura Kouichi
Second Department Of Internal Medecine Yokohama City University School Of Medicine
-
Yoshida Yoshinori
Department Of Cardiovascular Medicine Graduate School Of Medicine Kyoto University
-
Hidaka K
Department Of Bioscience National Cardiovascular Center Research Institute
-
Kimura Takeshi
Department Of Respiratory Medicine Graduate School Of Medicine Kyoto University
-
Tanno Kaoru
Division Of Cardiology Kobe City Medical Center General Hospital
-
Takanaka Kotoe
Department Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine
-
Sunagawa Yoichi
Division Of Translational Research Kyoto Medical Center National Hospital Organization
-
Tanaka Keiji
Intensive And Cardiac Care Unit Nippon Medical School
-
Kita Toru
Departments Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine
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Kawamoto Takahiro
Department Of Geriatric Medicine Graduate School Of Medicine Kyoto University
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Kawamura Teruhisa
Division Of Translational Research Kyoto Medical Center
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Kita Toru
Department Of Clinical Bio-regulatory Science Division Of Molecular Medicine For Adult And Geriatric
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Kita Toru
Department Of Cardiology Kyoto University
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Hasegawa Koji
Division Of Translational Research Clinical Research Institute Kyoto Medical Center National Hospita
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Hasegawa Koji
国立病院機構京都医療センター 展開医療研究部
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Kojima Tozo
Department Of Nephrology And Endocrinology University Of Tokyo Faculty Of Medicine
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Morimoto Takeshi
Kyoto University Hospital
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Kimura Takeshi
Department Of Cardiovascular Medicine Kyoto University Hospital
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Tanno Kaoru
Department Of Cardiology Kobe City Medical Center General Hospital
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Katsuya Tomohiro
The Department Of Geriatric Medicine Osaka University Medical School
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Fujita Masatoshi
Iii Div. Dept Of Intern. Med. Kyoto Univ.
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Kimura Takeshi
Department Of Cardiovascular Medicine Graduate School Of Medicine Kyoto University
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Kita Toru
Division Of Cardiology Kobe City Medical Center General Hospital
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Kudoh Takashi
Department Of Nuclear Medicine Kyoto University
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Fujita Masatoshi
Human Health Sciences Graduate School Of Medicine Kyoto University
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Shimatsu Akira
Division Of Endocrinology And Metabolism Clinical Research Institute For Endocrine Metabolic Disease
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Yoshida Yoshinori
Department Of Cardiology Kishiwada Tokushukai Hospital
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Kobayashi Toru
Second Department Of Internal Medicine Osaka University Medical School Center Of Adult Disease
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Kudoh Takashi
Department Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine
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Katoh Takao
Department Of Disease Control And Homeostasis Graduate School Of Medical Science Kanazawa University
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Morota Tetsuro
Department Of Cardiothoracic Surgery And Human Pathology The University Of Tokyo Graduate School Of
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Fujita Masatoshi
Dep. Of Human Health Sciences Graduate School Of Medicine Kyoto Univ.
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Kogure T
Department Of Internal Medicine And Cardiorenal Medicine Yokohama City University Graduate School Of
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Kita Toru
National Hospital Organization And Department Of Cardiovascular Medicine Graduate School Of Medicine
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Kawamura Tetsuya
Department Of Nephrology And Hypertension School Of Medicine Jikei University
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Shimatsu Akira
Clinical Res. Inst. National Hospital Organization Kyoto Medical Center Kyoto Jpn
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Tatsumi Koichiro
Department Of Respirology (b2) Graduate School Of Medicine Chiba University
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Kimura Takeshi
Department Of Respiratory Medicine Otsu Red Cross Hospital
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Morimoto Tatsuya
Division Of Molecular Medicine School Of Pharmaceutical Sciences University Of Shizuoka
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Hasegawa Koji
Department Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine
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Fujita Masatoshi
Department Of Human Health Sciences Division Of Bioinformatics And Chemical Genomics Graduate School
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Kita Toru
Division Of Translational Research Kyoto Medical Center National Hospital Organization
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Kimura Takeshi
Cardiovascular Center Yokosuka Kyosai Hospital
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Koyama Takashi
Cardiovascular Division Institute Of Clinical Medicine Graduate School Of Comprehensive Human Scienc
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Miyamoto Tadashi
Center For Medical Education And Clinical Epidemiology Unit Graduate School Of Medicine Kyoto Univer
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Fujita Masatoshi
Department Of Human Health Sciences Division Of Bioinformatics And Chemical Genomics Graduate School Of Pharmaceutical Sciences Kyoto University
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KIYOOKA Takahiko
Tokai University Hachioji Hospital
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Fujita Masatoshi
Human Health Sciences Graduate School Of Medicine Kyoto Univ.
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Shimatsu Akira
Clinical Res. Inst. Kyoto Medical Center National Hospital Organization
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Takaya Tomohide
Department of Cardiovascular Medicine, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University
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YOSHIDA Yoshinori
Department of Biomaterials Science, Osaka University Graduate School of Dentistry
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Sunagawa Yoichi
Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
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- PE-387 Global Expression Profiling of Hypertrophy-associated Genes Regulated by a Transcriptional Coactivatior, p300(Heart failure, basic-4 (M) PE65,Poster Session (English),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Societ
- OE-207 Histone Acetyltransferase Activity of p300 Is Required for the Promotion of Left Ventricular Remodeling Following Myocardial Infarction in Adult Mice(Cardiac function, basic/clinical-1 (M) OE35,Oral Presentation (English),The 70th Anniversary Annua
- 4 The Effects of Ubiquitin Ligase p300 on the Cardiac Myocytes Apoptosis(Signaling pathways that modulate differentiation and death in cardiovascular cells,Topic 6 (TP6) (M),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Societ
- PE-242 Simvastatin Improves Impairment of Left Ventricular Diastolic Filling in a Rat Model of Type II Diabetes with Obesity(Diabetes/Obesity/Metabolic syndrome-8 (H) PE41,Poster Session (English),The 70th Anniversary Annual Scientific Meeting of the Japa
- OJ-048 A Soluble Flk-1, an Endogenous Inhibitor of Vascular Endothelial Growth Factor, is Increased in Serum of Patients with Metabolic Syndrome(Diabetes/Obesity/Metabolic syndrome-3 (H) OJ8,Oral Presentation (Japanese),The 70th Anniversary Annual Scienti
- Epigallocatechin-3-gallate, a Major Polyphenolic Constituent of Green Tea, Induces Apoptosis in 3T3-L1 Preadipocytes After Induction of Differentiation(Diabetes/Obesity 3 (H), The 69th Annual Scientific Meeting of the Japanese Circulation Society)