Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species.

Autor:	Luo J; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Gao Q; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Qiu H; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Zhang S; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Zou W; School of Medicine South China University of Technology, 510006 Guangzhou, Guangdong, China., Wang P; School of Medical Imaging, Tianjin Medical University, 300203 Tianjin, China., Zhou L; Guangdong Beating Origin Regenerative Medicine Co., Ltd., 528231 Foshan, Guangdong, China., Liu L; Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, China., Xu F; Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, China., Li X; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Lin B; Guangdong Beating Origin Regenerative Medicine Co., Ltd., 528231 Foshan, Guangdong, China., Zeng R; Guangdong Provincial First Disabled Veterans Hospital, 510260 Guangzhou, Guangdong, China., Sun D; Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, 361102 Xiamen, Fujian, China., Cen J; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China., Zhuang J; Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, 510080 Guangzhou, Guangdong, China.
Jazyk:	angličtina
Zdroj:	Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2024 Feb 04; Vol. 29 (2), pp. 49.
DOI:	10.31083/j.fbl2902049
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. However, it should be noted that Lishi Zhou and Bin Lin are affiliated with Guangdong Beating Origin Regenerative Medicine Co., Ltd. Steps have been taken to ensure that their involvement in this research did not influence the objectivity and integrity of the study findings. (© 2024 The Author(s). Published by IMR Press.)
Databáze:	MEDLINE
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