Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes
Introduction: Heart failure is the final pathway for a wide spectrum of myocardial stress, including hypertension and myocardial infarction. However, the potential effects of metformin on cardiac hypertrophy are still unclear. Purpose: The purpose of this study was to investigate whether metformin l...
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| Language: | English |
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Elsevier
2021-10-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861321000682 |
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| author | Yoichi Sunagawa Kiyotaka Shimizu Ayumi Katayama Masafumi Funamoto Kana Shimizu Sari Nurmila Satoshi Shimizu Yusuke Miyazaki Yasufumi Katanasaka Koji Hasegawa Tatsuya Morimoto |
| author_facet | Yoichi Sunagawa Kiyotaka Shimizu Ayumi Katayama Masafumi Funamoto Kana Shimizu Sari Nurmila Satoshi Shimizu Yusuke Miyazaki Yasufumi Katanasaka Koji Hasegawa Tatsuya Morimoto |
| author_sort | Yoichi Sunagawa |
| collection | DOAJ |
| description | Introduction: Heart failure is the final pathway for a wide spectrum of myocardial stress, including hypertension and myocardial infarction. However, the potential effects of metformin on cardiac hypertrophy are still unclear. Purpose: The purpose of this study was to investigate whether metformin leads to suppression of hypertrophic responses in cardiomyocytes. Methods and results: To investigate whether metformin inhibited p300-histone acetyltransferase (HAT), we performed an in vitro HAT assay. Metformin directly inhibited p300-mediated acetylation of histone-H3K9. To examine the effects of metformin on hypertrophic responses, cardiomyocytes prepared from neonatal rats were treated with metformin and stimulated with saline or phenylephrine (PE), a α1-adrenergic agonist for 48 h. PE stimulus showed an increase in cell size, myofibrillar organization, expression of the endogenous atrial natriuretic factor and brain natriuretic peptide genes, and acetylation of histone-H3K9 compared with saline-treated cells. These PE-induced changes were inhibited by metformin. Next, to examine the effect of metformin on p300-mediated hypertrophy, cardiomyocytes were transfected with expression vector of p300. Metformin significantly suppressed p300-induced hypertrophic responses and acetylation of histone-H3K9. Conclusions: The study demonstrates that metformin can suppress PE-induced and p300-mediated hypertrophic responses. Metformin may be useful for the treatment of patients with diabetes and heart failure. |
| first_indexed | 2024-12-22T11:17:54Z |
| format | Article |
| id | doaj.art-76477e78d0144ae595612eeb38ae8a9b |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-22T11:17:54Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-76477e78d0144ae595612eeb38ae8a9b2022-12-21T18:27:57ZengElsevierJournal of Pharmacological Sciences1347-86132021-10-011472169175Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytesYoichi Sunagawa0Kiyotaka Shimizu1Ayumi Katayama2Masafumi Funamoto3Kana Shimizu4Sari Nurmila5Satoshi Shimizu6Yusuke Miyazaki7Yasufumi Katanasaka8Koji Hasegawa9Tatsuya Morimoto10Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, Japan; Shizuoka General Hospital, Shizuoka, 420-8527, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, Japan; Shizuoka General Hospital, Shizuoka, 420-8527, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, Japan; Shizuoka General Hospital, Shizuoka, 420-8527, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, 612-8555, Japan; Shizuoka General Hospital, Shizuoka, 420-8527, Japan; Corresponding author. Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. Fax: +81 54 264 5744.Introduction: Heart failure is the final pathway for a wide spectrum of myocardial stress, including hypertension and myocardial infarction. However, the potential effects of metformin on cardiac hypertrophy are still unclear. Purpose: The purpose of this study was to investigate whether metformin leads to suppression of hypertrophic responses in cardiomyocytes. Methods and results: To investigate whether metformin inhibited p300-histone acetyltransferase (HAT), we performed an in vitro HAT assay. Metformin directly inhibited p300-mediated acetylation of histone-H3K9. To examine the effects of metformin on hypertrophic responses, cardiomyocytes prepared from neonatal rats were treated with metformin and stimulated with saline or phenylephrine (PE), a α1-adrenergic agonist for 48 h. PE stimulus showed an increase in cell size, myofibrillar organization, expression of the endogenous atrial natriuretic factor and brain natriuretic peptide genes, and acetylation of histone-H3K9 compared with saline-treated cells. These PE-induced changes were inhibited by metformin. Next, to examine the effect of metformin on p300-mediated hypertrophy, cardiomyocytes were transfected with expression vector of p300. Metformin significantly suppressed p300-induced hypertrophic responses and acetylation of histone-H3K9. Conclusions: The study demonstrates that metformin can suppress PE-induced and p300-mediated hypertrophic responses. Metformin may be useful for the treatment of patients with diabetes and heart failure.http://www.sciencedirect.com/science/article/pii/S1347861321000682Metforminp300CardiomyocyteHypertrophyHistone acetyltransferase |
| spellingShingle | Yoichi Sunagawa Kiyotaka Shimizu Ayumi Katayama Masafumi Funamoto Kana Shimizu Sari Nurmila Satoshi Shimizu Yusuke Miyazaki Yasufumi Katanasaka Koji Hasegawa Tatsuya Morimoto Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes Journal of Pharmacological Sciences Metformin p300 Cardiomyocyte Hypertrophy Histone acetyltransferase |
| title | Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes |
| title_full | Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes |
| title_fullStr | Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes |
| title_full_unstemmed | Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes |
| title_short | Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes |
| title_sort | metformin suppresses phenylephrine induced hypertrophic responses by inhibiting p300 hat activity in cardiomyocytes |
| topic | Metformin p300 Cardiomyocyte Hypertrophy Histone acetyltransferase |
| url | http://www.sciencedirect.com/science/article/pii/S1347861321000682 |
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