球形脂联素通过 Pink1/Parkin 介导的线粒体自噬诱导保护肝细胞免受间歇性低氧诱导的损伤。
Globular adiponectin protects hepatocytes against intermittent hypoxia-induced injury via Pink1/Parkin-mediated mitophagy induction.
机构信息
Department of Pulmonary and Critical Care Medicine, ZhongDa Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China.
Department of Emergency, Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing, 210029, China.
出版信息
Sleep Breath. 2022 Sep;26(3):1389-1397. doi: 10.1007/s11325-021-02508-8. Epub 2021 Oct 26.
PURPOSE
This study sought to determine the effect of Pink1/Parkin-mediated mitophagy on liver cells exposed to intermittent hypoxia (IH) and the roles of globular adiponectin (gAPN).
METHODS
The hepatocyte model of IH was established. Cell apoptosis was assessed using flow cytometry. Mitochondrial membrane potential (MMP) level was determined using JC-1, and mitophagy was assessed using a confocal laser. Mitochondrial injury associated protein levels of bax and bcl-2, and protein levels of Pink1 and Parkin were evaluated via western blotting. We downregulated Parkin expression by transfecting the cells with Parkin siRNA.
RESULTS
Pink1 and Parkin protein levels, mitophagy, and cell apoptosis rate were high, while the MMP level and protein level ratio of bcl-2/bax were low in IH-treated hepatocyte. gAPN upregulated Pink1 and Parkin protein levels, MMP level, protein level ratio of bcl-2/bax, and mitophagy while it reduced the rate of cell apoptosis in IH-treated hepatocytes. Inhibiting Parkin expression significantly reduced mitophagy and increased mitochondrial injury and the rate of hepatocyte apoptosis under IH or IH with gAPN.
CONCLUSION
gAPN alleviated IH-induced mitochondrial injury and hepatocyte apoptosis by upregulating Pink1/Parkin-mediated mitophagy.
目的
本研究旨在探讨 Pink1/Parkin 介导的线粒体自噬对间歇性低氧（IH）暴露的肝细胞的影响，以及球形脂联素（gAPN）的作用。
方法
建立肝细胞 IH 模型。采用流式细胞术评估细胞凋亡。使用 JC-1 测定线粒体膜电位（MMP）水平，并用共聚焦激光评估线粒体自噬。通过 Western blot 评估 bax 和 bcl-2 的线粒体损伤相关蛋白水平以及 Pink1 和 Parkin 的蛋白水平。我们通过转染 Parkin siRNA 下调 Parkin 表达。
结果
在 IH 处理的肝细胞中，Pink1 和 Parkin 蛋白水平、线粒体自噬和细胞凋亡率较高，而 MMP 水平和 bcl-2/bax 的蛋白水平比值较低。gAPN 上调了 IH 处理的肝细胞中的 Pink1 和 Parkin 蛋白水平、MMP 水平、bcl-2/bax 的蛋白水平比值和线粒体自噬，同时降低了细胞凋亡率。抑制 Parkin 表达可显著减少线粒体自噬，增加线粒体损伤和 IH 或 IH 加 gAPN 下的肝细胞凋亡率。
结论
gAPN 通过上调 Pink1/Parkin 介导的线粒体自噬减轻 IH 诱导的线粒体损伤和肝细胞凋亡。
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