Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Environ Pollut. 2020 Jan;256:113430. doi: 10.1016/j.envpol.2019.113430. Epub 2019 Oct 23.
Silver nanoparticles (AgNPs) are inevitably released into the environment owing to their widespread applications in industry and medicine. The potential of their toxicity has aroused a great concern. Previous studies have shown that AgNPs exposure in HepG2 cells is primarily related to the damage of mitochondria, which includes induction of mitochondrial swelling and increase of intracellular levels of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential and induction of apoptosis through a mitochondrial pathway. In this study, the effects of AgNPs exposure in HepG2 cells on mitochondrial dynamics and biogenesis were investigated. AgNPs were found to induce mitochondrial morphological and structural alterations. The expressions of key proteins (Drp1, Fis1, OPA1, Mff, Mfn1, and Mfn2) related to mitochondrial fission/fusion event were changed. Especially the expression of fission-related protein 1 (p-Drp1) (Ser616) was significantly up-regulated, whereas the expression of mitochondrial biogenesis protein (PGC-1α) was reduced in AgNP-treated cells. Concomitantly, the expression of autophagy marker proteins (LC3B and p62) was increased. The results suggested that AgNPs could trigger cytotoxicity by targeting the mitochondria, resulting in the disruption of mitochondrial function, damage to the mitochondrial structure and morphology, interfering in mitochondrial dynamics and biogenesis. The mitochondria could be a critical target of AgNPs in cells. The functions of mitochondria could be used for assessing the cytotoxic effects associated with AgNPs in cells.
由于其在工业和医学中的广泛应用，银纳米颗粒（AgNPs）不可避免地会释放到环境中。其潜在的毒性引起了极大的关注。先前的研究表明，AgNPs 在 HepG2 细胞中的暴露主要与线粒体损伤有关，包括诱导线粒体肿胀和增加细胞内活性氧（ROS）水平、线粒体膜电位崩溃和通过线粒体途径诱导细胞凋亡。在本研究中，研究了 AgNPs 在 HepG2 细胞中暴露对线粒体动力学和生物发生的影响。发现 AgNPs 诱导线粒体形态和结构改变。与线粒体分裂/融合事件相关的关键蛋白（Drp1、Fis1、OPA1、Mff、Mfn1 和 Mfn2）的表达发生变化。特别是分裂相关蛋白 1（p-Drp1）（Ser616）的表达明显上调，而 AgNP 处理细胞中与线粒体生物发生相关的蛋白（PGC-1α）的表达减少。同时，自噬标记蛋白（LC3B 和 p62）的表达增加。结果表明，AgNPs 可以通过靶向线粒体引发细胞毒性，导致线粒体功能障碍、线粒体结构和形态损伤、干扰线粒体动力学和生物发生。线粒体可能是细胞中 AgNPs 的一个关键靶标。线粒体的功能可用于评估与细胞中 AgNPs 相关的细胞毒性作用。
