Department of Cardiology, Affiliated Hengyang Hospital, Southern Medical University (Hengyang Central Hospital), Hengyang, China.
J Recept Signal Transduct Res. 2021 Oct;41(5):451-456. doi: 10.1080/10799893.2020.1825488. Epub 2020 Oct 5.
Inflammation has been acknowledged as one of the pathological alterations in various cardiovascular disorders. Parkin has been found to be associated with mitochondrial protection. In the present study, we explored the influence of Parkin overexpression on cardiomyocyte induced by LPS-mediated inflammation response. Our results demonstrated that cardiomyocyte viability was reduced and apoptotic rate was increased upon LPS treatment, an effect that may be caused by cardiomyocyte oxidative stress. At the molecular levels, LPS treatment promoted ROS production, a result that was followed by a drop in the levels of anti-oxidants. Interestingly, Parkin overexpression significantly promoted cardiomyocyte survival and this cardioprotective was attributable to the anti-oxidative property. Parkin overexpression enhanced the expression of anti-oxidative factors such as GSH, SOD and GPX, resulting into depressed ROS production. Further, we found that Parkin modulated cellular anti-oxidative capacity through the Nrf2/ARE signaling pathway. This finding demonstrates that oxidative stress could be considered as the core of inflammation response. Further, therapeutic approaches targeting Parkin would improve cardiomyocyte anti-oxidative capacity through activating Nrf2/ARE signaling pathway.
炎症已被公认为各种心血管疾病的病理改变之一。Parkin 已被发现与线粒体保护有关。在本研究中，我们探讨了 Parkin 过表达对 LPS 介导的炎症反应诱导的心肌细胞的影响。我们的结果表明，LPS 处理可降低心肌细胞活力并增加细胞凋亡率，这可能是由心肌细胞氧化应激引起的。在分子水平上，LPS 处理促进了 ROS 的产生，随后抗氧化剂的水平下降。有趣的是，Parkin 过表达显著促进了心肌细胞的存活，这种心脏保护作用归因于其抗氧化特性。Parkin 过表达增强了 GSH、SOD 和 GPX 等抗氧化因子的表达，从而抑制了 ROS 的产生。此外，我们发现 Parkin 通过 Nrf2/ARE 信号通路调节细胞抗氧化能力。这一发现表明氧化应激可以被认为是炎症反应的核心。此外，针对 Parkin 的治疗方法可以通过激活 Nrf2/ARE 信号通路来提高心肌细胞的抗氧化能力。
