Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Toxicol In Vitro. 2013 Sep;27(6):1762-70. doi: 10.1016/j.tiv.2013.05.004. Epub 2013 May 17.
Exposure to higher levels of air pollution particulate matter (PM) with an aerodynamic diameter of less than 2.5 μm (PM2.5) links with an increased risk of cardiovascular and respiratory deaths and hospital admission as well as lung cancer. Although the mechanism underlying the correlation between PM2.5 exposure and adverse effects has not fully elucidated, PM2.5-induced oxidative stress has been considered as an important molecular mechanism of PM2.5-mediated toxicity. In this work, human lung epithelial A549 cells were used to further investigate the biological effects of PM2.5 on autophagy. The cell viability showed both time- and concentration-dependent decrease when exposure to PM2.5, which can be attributed to increase of the levels of extracellular lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) generation in A549 cells. Moreover, PM2.5-induced oxidative damage in A549 cells was observed through the alteration of superoxide dismutase (SOD) and catalase (CAT) activities compared to the unexposed control cells. PM2.5-induced autophagy was indicated by an increase in microtubule-associated protein light chain-3 (LC3) puncta, and accumulation of LC3 in both time- and concentration-dependent manner. PM2.5-induced mRNA expression of autophagy-related protein Atg5 and Beclin1 was also observed compared with those of the unexposed control cells. These results suggest the possibility that PM2.5-induced oxidative stress probably plays a key role in autophagy in A549 cells, which may contribute to PM2.5-induced impairment of pulmonary function.
暴露于空气动力学直径小于 2.5μm 的更高水平的空气污染物（PM）与心血管和呼吸道死亡以及住院率以及肺癌的风险增加有关。尽管 PM2.5 暴露与不良影响之间的相关性的机制尚未完全阐明，但 PM2.5 诱导的氧化应激已被认为是 PM2.5 介导的毒性的重要分子机制。在这项工作中，使用人肺上皮 A549 细胞进一步研究了 PM2.5 对自噬的生物学影响。当暴露于 PM2.5 时，细胞活力显示出时间和浓度依赖性降低，这归因于 A549 细胞中外乳酸脱氢酶（LDH）释放水平和细胞内活性氧（ROS）生成的增加。此外，与未暴露的对照细胞相比，PM2.5 诱导的 A549 细胞中的氧化损伤通过超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性的改变来观察到。PM2.5 诱导的自噬通过微管相关蛋白轻链-3（LC3）斑点的增加以及 LC3 的时间和浓度依赖性积累来指示。与未暴露的对照细胞相比，还观察到 PM2.5 诱导的自噬相关蛋白 Atg5 和 Beclin1 的 mRNA 表达增加。这些结果表明，PM2.5 诱导的氧化应激可能在 A549 细胞中的自噬中起关键作用，这可能导致 PM2.5 诱导的肺功能损害。
