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Oxidative stress-induced cardiomyocyte apoptosis is associated with dysregulated Akt/p53 signaling pathway
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-05-27 , DOI: 10.1080/10799893.2020.1772297
Nan Zheng 1 , Han Li 2 , Xi Wang 3 , Zaixian Zhao 3 , Dongkai Shan 1
Affiliation  

Abstract Oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases. In the present study, we explored the mechanism underlying oxidative stress-mediated cardiomyocyte apoptosis with a focus on the Akt-p53 signaling pathway. In vitro, cardiomyocyte was cultured with different concentrations of hydrogen peroxide. Then, cardiomyocyte viability, apoptosis rate and signaling pathway were analyzed through ELISA, immunofluorescence, qPCR and western blots. The results indicated that oxidative stress caused cardiomyocyte apoptosis in a dose-dependent manner. Mechanistically, oxidative stress inhibited cardiomyocyte glucose metabolism and promoted lactic acid accumulation. Besides, oxidative stress triggered calcium overload in cardiomyocyte. Finally, we found that oxidative stress inhibited the activity of Akt pathway while activated p53 signaling pathway. Genetic knockdown of p53 abolished oxidative stress-mediated cardiomyocyte injury and death through regulating the expressions and activities of caspase-3 and Bax. Altogether, our results illustrate that oxidative stress is associated with cardiomyocyte apoptosis through a mechanism involving dysregulated Akt/p53 signaling pathway.

中文翻译:

氧化应激诱导的心肌细胞凋亡与 Akt/p53 信号通路失调有关

摘要 氧化应激可能在不同类型心血管疾病的心脏和血管异常中起关键作用。在本研究中,我们探索了氧化应激介导的心肌细胞凋亡的机制,重点是 Akt-p53 信号通路。在体外,心肌细胞用不同浓度的过氧化氢培养。然后,通过ELISA、免疫荧光、qPCR和蛋白质印迹分析心肌细胞活力、凋亡率和信号通路。结果表明,氧化应激以剂量依赖性方式引起心肌细胞凋亡。从机制上讲,氧化应激抑制心肌细胞葡萄糖代谢并促进乳酸积累。此外,氧化应激引发心肌细胞钙超载。最后,我们发现氧化应激抑制了Akt通路的活性,同时激活了p53信号通路。p53 的基因敲低通过调节 caspase-3 和 Bax 的表达和活性消除了氧化应激介导的心肌细胞损伤和死亡。总之,我们的结果表明氧化应激与心肌细胞凋亡有关,其机制涉及 Akt/p53 信号通路失调。
更新日期:2020-05-27
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