Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells
Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells
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DOI：
10.3390/cells8101241
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发表时间：
2019-10-01
期刊：
影响因子：
6
通讯作者：
Ren, Zhuqing
中科院分区：
文献类型：
--
作者：
Tan, Yanjie;Jin, Yi;Ren, Zhuqing
非酒精性脂肪性肝病（NAFLD）是全球最常见的肝病之一。活性氧（ROS）作为细胞中的强氧化剂，已被证明可促进NAFLD的发展。以往的研究报道，对于ROS诱导的细胞氧化应激，促进脂滴（LD）的积累与细胞的抗氧化过程。然而，LD在缓解细胞氧化应激中的调节作用知之甚少。在这里，我们表明，Perilipin 5（PLIN 5），一种与HepG 2细胞中的ROS水平降低和线粒体功能改善有关的关键LD蛋白。过氧化氢或脂多糖（LPS）处理的细胞中PLIN 5的mRNA和蛋白水平均显著增加（p < 0.05）。此外，PLIN 5的过表达促进了LD形成和E-LD接触，降低了细胞ROS水平并上调了线粒体功能相关基因如考克斯和CS。与此同时，敲低PLIN 5显示出相反的效果。此外，我们确定细胞氧化应激通过JNK-p38-ATF途径上调PLIN 5表达。这项研究表明PLIN 5的上调是细胞应对应激的一种生存策略。PLIN 5可能是NAFLD的潜在治疗靶点。
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria-LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria-LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD.