Zenglv Fumai Granule protects cardiomyocytes against hypoxia/reoxygenation-induced apoptosis via inhibiting TRIM28 expression
العنوان: | Zenglv Fumai Granule protects cardiomyocytes against hypoxia/reoxygenation-induced apoptosis via inhibiting TRIM28 expression |
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المؤلفون: | Zhao Hongyu, Xin-Yu Liu, Zhang Xiaohua, Lin Di, Liu Shurong, Feng Qian, Wang Yu |
المصدر: | Molecular Medicine Reports |
بيانات النشر: | Spandidos Publications, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, GPX1, Myocardial Reperfusion Injury, Tripartite Motif-Containing Protein 28, Biochemistry, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Zenglv Fumai Granule, Genetics, Humans, Myocytes, Cardiac, Molecular Biology, chemistry.chemical_classification, Gene knockdown, Reactive oxygen species, glutathione peroxidase 1, Oncogene, Chemistry, TRIM28, Glutathione peroxidase, apoptosis, Articles, Cell cycle, Cell biology, 030104 developmental biology, Gene Expression Regulation, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Molecular Medicine, Drugs, Chinese Herbal |
الوصف: | Myocardial ischemia/reperfusion (MIR) injury, which occurs following acute myocardial infarction, can cause secondary damage to the heart. Tripartite interaction motif (TRIM) proteins, a class of E3 ubiquitin ligases, have been recognized as critical regulators in MIR injury. Zenglv Fumai Granule (ZFG) is a clinical prescription for the treatment of sick sinus syndrome, a disease that is associated with MIR injury. The present study aimed to investigate the effect of ZFG on MIR injury and to determine whether ZFG exerts its effects via regulation of TRIM proteins. In order to establish an in vitro MIR model, human cardiomyocyte cell line AC16 was cultured under hypoxia for 5 h and then under normal conditions for 1 h. Following hypoxia/reoxygenation (H/R) treatment, these cells were cultured with different ZFG concentrations. ZFG notably inhibited H/R-induced cardiomyocyte apoptosis. The expression levels of four TRIM proteins, TRIM7, TRIM14, TRIM22 and TRIM28, were also detected. These four proteins were significantly upregulated in H/R-injured cardiomyocytes, whereas their expression was inhibited following ZFG treatment. Moreover, TRIM28 knockdown inhibited H/R-induced cardiomyocyte apoptosis, whereas TRIM28 overexpression promoted apoptosis and generation of reactive oxygen species (ROS) in cardiomyocytes. However, the effects of TRIM28 overexpression were limited by the action of ROS inhibitor N-acetyl-L-cysteine. In addition, the mRNA and protein levels of antioxidant enzyme glutathione peroxidase (GPX)1 were significantly downregulated in H/R-injured cardiomyocytes. TRIM28 knockdown restored GPX1 protein levels but had no effect on mRNA expression levels. Co-immunoprecipitation and ubiquitination assays demonstrated that TRIM28 negatively regulated GPX1 via ubiquitination. In sum, the present study revealed that ZFG attenuated H/R-induced cardiomyocyte apoptosis by regulating the TRIM28/GPX1/ROS pathway. ZFG and TRIM28 offer potential therapeutic options for the treatment of MIR injury. |
تدمد: | 1791-3004 1791-2997 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1490dcd15ae43e792bc6a9b9ec6d8798Test https://doi.org/10.3892/mmr.2020.11810Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....1490dcd15ae43e792bc6a9b9ec6d8798 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 17913004 17912997 |
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