Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species
Background: Myogenin is well known as a crucial transcription factor in skeletal muscle development, yet its other biological functions remain unexplored. Previous research showed that myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocyt...
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| Format: | Article |
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IMR Press
2024-02-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902049 |
| _version_ | 1797290428849979392 |
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| author | Jing Luo Qiang Gao Hailong Qiu Shuai Zhang Wanwan Zou Ping Wang Lishi Zhou Lingling Liu Feng Xu Xiaohua Li Bin Lin Rong Zeng Daoheng Sun Jianzheng Cen Jian Zhuang |
| author_facet | Jing Luo Qiang Gao Hailong Qiu Shuai Zhang Wanwan Zou Ping Wang Lishi Zhou Lingling Liu Feng Xu Xiaohua Li Bin Lin Rong Zeng Daoheng Sun Jianzheng Cen Jian Zhuang |
| author_sort | Jing Luo |
| collection | DOAJ |
| description | Background: Myogenin is well known as a crucial transcription factor in skeletal muscle development, yet its other biological functions remain unexplored. Previous research showed that myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes, and offered a new perspective on myogenin’s role in cardioprotection. However, the detailed mechanism of this cardioprotection, especially under oxidative stress, is still unclear. Methods: In this study, hydrogen peroxide (H2O2) was used to generate reactive oxygen species in myogenin-overexpressing cardiomyocytes. The apoptosis was examined by flow cytometry. Transcriptome sequencing (RNA-seq) was performed to identify genes regulated by myogenin. Western blotting was used to detect the protein level of DUSP13 and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). The dual-luciferase reporter assay and ChIP assay were used to confirm the binding of myogenin to the promoter region of DUSP13. DUSP13 overexpression and knockdown assays were performed to study its anti-apoptotic role. Results: Flow cytometry analysis of apoptosis showed that overexpressing myogenin for 24 and 48 hours decreased the apoptotic ratio by 47.9% and 63.5%, respectively, compared with untreated controls. Transcriptome sequencing performed on cardiomyocytes that expressed myogenin for different amounts of time (6, 12, 24, and 48 hours) identified DUSP13 as being up-regulated by myogenin. Western blotting showed that overexpression of myogenin increased the expression of DUSP13 and decreased the phosphorylation level of p38 MAPK. A dual-luciferase reporter assay proved that myogenin bound directly to the promoter region of DUSP13 and led to strong relative luciferase activity. Direct expression of DUSP13A and DUSP13B significantly reduced the rates of apoptosis and necrosis in cells treated with H2O2. Knockdown of DUSP13B significantly increased the rate of apoptosis in cells treated with H2O2. Conclusions: The present findings suggest that myogenin might attenuate apoptosis induced by reactive oxygen species by up-regulating DUSP13 and inactivating the p38 MAPK pathway. |
| first_indexed | 2024-03-07T19:22:15Z |
| format | Article |
| id | doaj.art-c474fe2199ad4fb0a0196b49dd73f953 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-07T19:22:15Z |
| publishDate | 2024-02-01 |
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| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-c474fe2199ad4fb0a0196b49dd73f9532024-02-29T09:53:15ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-02-012924910.31083/j.fbl2902049S2768-6701(23)01152-8Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen SpeciesJing Luo0Qiang Gao1Hailong Qiu2Shuai Zhang3Wanwan Zou4Ping Wang5Lishi Zhou6Lingling Liu7Feng Xu8Xiaohua Li9Bin Lin10Rong Zeng11Daoheng Sun12Jianzheng Cen13Jian Zhuang14Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaSchool of Medicine South China University of Technology, 510006 Guangzhou, Guangdong, ChinaSchool of Medical Imaging, Tianjin Medical University, 300203 Tianjin, ChinaGuangdong Beating Origin Regenerative Medicine Co., Ltd., 528231 Foshan, Guangdong, ChinaPen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, ChinaPen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaGuangdong Beating Origin Regenerative Medicine Co., Ltd., 528231 Foshan, Guangdong, ChinaGuangdong Provincial First Disabled Veterans Hospital, 510260 Guangzhou, Guangdong, ChinaPen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaBackground: Myogenin is well known as a crucial transcription factor in skeletal muscle development, yet its other biological functions remain unexplored. Previous research showed that myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes, and offered a new perspective on myogenin’s role in cardioprotection. However, the detailed mechanism of this cardioprotection, especially under oxidative stress, is still unclear. Methods: In this study, hydrogen peroxide (H2O2) was used to generate reactive oxygen species in myogenin-overexpressing cardiomyocytes. The apoptosis was examined by flow cytometry. Transcriptome sequencing (RNA-seq) was performed to identify genes regulated by myogenin. Western blotting was used to detect the protein level of DUSP13 and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). The dual-luciferase reporter assay and ChIP assay were used to confirm the binding of myogenin to the promoter region of DUSP13. DUSP13 overexpression and knockdown assays were performed to study its anti-apoptotic role. Results: Flow cytometry analysis of apoptosis showed that overexpressing myogenin for 24 and 48 hours decreased the apoptotic ratio by 47.9% and 63.5%, respectively, compared with untreated controls. Transcriptome sequencing performed on cardiomyocytes that expressed myogenin for different amounts of time (6, 12, 24, and 48 hours) identified DUSP13 as being up-regulated by myogenin. Western blotting showed that overexpression of myogenin increased the expression of DUSP13 and decreased the phosphorylation level of p38 MAPK. A dual-luciferase reporter assay proved that myogenin bound directly to the promoter region of DUSP13 and led to strong relative luciferase activity. Direct expression of DUSP13A and DUSP13B significantly reduced the rates of apoptosis and necrosis in cells treated with H2O2. Knockdown of DUSP13B significantly increased the rate of apoptosis in cells treated with H2O2. Conclusions: The present findings suggest that myogenin might attenuate apoptosis induced by reactive oxygen species by up-regulating DUSP13 and inactivating the p38 MAPK pathway.https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902049myogenindusp13reactive oxygen speciesp38 mapk pathwayapoptosiscardiomyocyte |
| spellingShingle | Jing Luo Qiang Gao Hailong Qiu Shuai Zhang Wanwan Zou Ping Wang Lishi Zhou Lingling Liu Feng Xu Xiaohua Li Bin Lin Rong Zeng Daoheng Sun Jianzheng Cen Jian Zhuang Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species Frontiers in Bioscience-Landmark myogenin dusp13 reactive oxygen species p38 mapk pathway apoptosis cardiomyocyte |
| title | Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species |
| title_full | Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species |
| title_fullStr | Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species |
| title_full_unstemmed | Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species |
| title_short | Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species |
| title_sort | myogenin regulates dusp13 to inhibit apoptosis induced by reactive oxygen species |
| topic | myogenin dusp13 reactive oxygen species p38 mapk pathway apoptosis cardiomyocyte |
| url | https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902049 |
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