6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure
Hypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure,...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/9/2232 |
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| author | Yuto Kawase Yoichi Sunagawa Kana Shimizu Masafumi Funamoto Toshihide Hamabe-Horiike Yasufumi Katanasaka Satoshi Shimizu Philip Hawke Kiyoshi Mori Maki Komiyama Koji Hasegawa Tatsuya Morimoto |
| author_facet | Yuto Kawase Yoichi Sunagawa Kana Shimizu Masafumi Funamoto Toshihide Hamabe-Horiike Yasufumi Katanasaka Satoshi Shimizu Philip Hawke Kiyoshi Mori Maki Komiyama Koji Hasegawa Tatsuya Morimoto |
| author_sort | Yuto Kawase |
| collection | DOAJ |
| description | Hypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure, and may be a target for heart failure therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects; however, its effect on cardiovascular diseases has not been investigated. One micromolar of 6-shogaol suppressed phenylephrine (PE)-induced increases in cardiomyocyte hypertrophy in rat primary cultured cardiomyocytes. In rat primary cultured cardiac fibroblasts, 6-shogaol suppressed transforming growth factor-beta (TGF-β)-induced increases in L-proline incorporation. It also blocked PE- and TGF-β-induced increases in histone H3K9 acetylation in the same cells and in vitro. An in vitro p300-HAT assay revealed that 6-shogaol suppressed histone acetylation. The mice underwent transverse aortic constriction (TAC) surgery, and were administered 0.2 or 1 mg/kg of 6-shogaol daily for 8 weeks. 6-shogaol prevented TAC-induced systolic dysfunction and cardiac hypertrophy in a dose-dependent manner. Furthermore, it also significantly inhibited TAC-induced increases in histone H3K9 acetylation. These results suggest that 6-shogaol may ameliorate heart failure through a variety of mechanisms, including the inhibition of p300-HAT activity. |
| first_indexed | 2024-03-11T04:09:58Z |
| format | Article |
| id | doaj.art-49f78a98a8964548a97db7ff370fbae8 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T04:09:58Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-49f78a98a8964548a97db7ff370fbae82023-11-17T23:30:56ZengMDPI AGNutrients2072-66432023-05-01159223210.3390/nu150922326-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart FailureYuto Kawase0Yoichi Sunagawa1Kana Shimizu2Masafumi Funamoto3Toshihide Hamabe-Horiike4Yasufumi Katanasaka5Satoshi Shimizu6Philip Hawke7Kiyoshi Mori8Maki Komiyama9Koji Hasegawa10Tatsuya Morimoto11Division 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, 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, JapanDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, JapanLaboratory of Scientific English, 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 Translational Research, National Hospital Organization Kyoto Medical Center, 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, JapanHypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure, and may be a target for heart failure therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects; however, its effect on cardiovascular diseases has not been investigated. One micromolar of 6-shogaol suppressed phenylephrine (PE)-induced increases in cardiomyocyte hypertrophy in rat primary cultured cardiomyocytes. In rat primary cultured cardiac fibroblasts, 6-shogaol suppressed transforming growth factor-beta (TGF-β)-induced increases in L-proline incorporation. It also blocked PE- and TGF-β-induced increases in histone H3K9 acetylation in the same cells and in vitro. An in vitro p300-HAT assay revealed that 6-shogaol suppressed histone acetylation. The mice underwent transverse aortic constriction (TAC) surgery, and were administered 0.2 or 1 mg/kg of 6-shogaol daily for 8 weeks. 6-shogaol prevented TAC-induced systolic dysfunction and cardiac hypertrophy in a dose-dependent manner. Furthermore, it also significantly inhibited TAC-induced increases in histone H3K9 acetylation. These results suggest that 6-shogaol may ameliorate heart failure through a variety of mechanisms, including the inhibition of p300-HAT activity.https://www.mdpi.com/2072-6643/15/9/22326-shogaolp300histone acetyltransferasecardiac remodelingheart failure |
| spellingShingle | Yuto Kawase Yoichi Sunagawa Kana Shimizu Masafumi Funamoto Toshihide Hamabe-Horiike Yasufumi Katanasaka Satoshi Shimizu Philip Hawke Kiyoshi Mori Maki Komiyama Koji Hasegawa Tatsuya Morimoto 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure Nutrients 6-shogaol p300 histone acetyltransferase cardiac remodeling heart failure |
| title | 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure |
| title_full | 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure |
| title_fullStr | 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure |
| title_full_unstemmed | 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure |
| title_short | 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure |
| title_sort | 6 shogaol an active component of ginger inhibits p300 histone acetyltransferase activity and attenuates the development of pressure overload induced heart failure |
| topic | 6-shogaol p300 histone acetyltransferase cardiac remodeling heart failure |
| url | https://www.mdpi.com/2072-6643/15/9/2232 |
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