Muscone ameliorates myocardial ischemia‒reperfusion injury by promoting myocardial glycolysis

作者：Xin Gu, Neng Bao, Jing Zhang, Guangyi Huang, Xiaodong Zhang, Zhixuan Zhang, Yinqiang Du, Haoyu Meng, Jia‐Bao Liu, Peng Wu, Xiaoyan Wang, Guangyan Wang · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e22154 · 被引用次数：13 · 研究领域：Cardiac Ischemia and Reperfusion、Sirtuins and Resveratrol in Medicine、Adipokines, Inflammation, and Metabolic Diseases

Objective: The incidence of acute myocardial infarction (AMI) is increasing yearly. With the use of thrombolysis or percutaneous coronary intervention (PCI), the mortality rate of acute myocardial infarction has been significantly reduced. However, reperfusion can cause additional myocardial injury. There is still a lack of effective drugs to treat I/R injury, and it is urgent to find new therapeutic drugs. Methods: . Additionally, the gene expression levels of the PUMA and p53 were analyzed by qRT‒PCR. Molecular docking was used to evaluate the binding energy between Muscone and NLRP3-related proteins. Immunoblotting and qRT‒PCR were used to assess the expression levels of NLRP3 signaling pathway-related proteins (NLRP3, ASC, and Caspase-1) and the NLRP3 gene, respectively. Moreover, the extracellular acidification rate of AC16 cells was measured using the Seahorse system to evaluate glycolysis levels after Muscone treatment. The expression of the key glycolytic enzyme PKM2 was analyzed by immunoblotting and qRT‒PCR. Finally, ChIP‒qPCR was performed to determine the levels of histone modifications (H3K4me3, H3K27me3, and H2AK119Ub) in the PKM2 promoter region. Results: GO functional enrichment analysis revealed that muscone was involved in regulating the biological processes (BP) of AMI, which mainly included negative regulation of the apoptosis signaling pathway, the response to lipopolysaccharide, and blood pressure regulation. The cellular components (CC) involved in musc...