Huang Qingyu, Zhang Jie, Peng Siyuan, Tian Meiping, Chen Jinsheng, Shen Heqing
Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China.
J Appl Toxicol. 2014 Jun;34(6):675-87. doi: 10.1002/jat.2910. Epub 2013 Aug 14.
Exposure to airborne particulate matter (PM)2.5, a PM with aerodynamic diameter of less than 2.5 µm, is known to be associated with a variety of adverse health effects. However, the molecular mechanisms involved in fine PM toxicity are still not well characterized. The present study aims to provide new insights into the cytotoxicity of PM2.5 on human lung epithelial cells (A549) at the proteomic level. Two-dimensional difference gel electrophoresis revealed a total of 27 protein spots, whose abundance were significantly altered in A549 cells exposed to water-soluble PM2.5 extracts (WSPE). Among these, 12 spots were upregulated while 15 were downregulated. Twenty-two proteins were further identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass/mass spectrometry and database search. The results revealed that oxidative stress, metabolic disturbance, dysregulation of signal transduction, aberrant protein synthesis and degradation, as well as cytoskeleton disorganization are major factors contributing to WSPE-mediated toxicity in human lung cells. It is further proposed that induction of apoptosis through p53, c-Myc and p21 pathways may be one of the key toxicological events occurred in A549 cells under WSPE stress. The data obtained here will aid our understanding of the toxic mechanisms related to PM2.5, and develop useful biomarkers indicative of inhalable PM2.5 exposure.
暴露于空气动力学直径小于2.5微米的细颗粒物(PM)2.5已知与多种不良健康影响相关。然而,细颗粒物毒性所涉及的分子机制仍未得到充分表征。本研究旨在在蛋白质组学水平上为PM2.5对人肺上皮细胞(A549)的细胞毒性提供新的见解。二维差异凝胶电泳显示共有27个蛋白点,其丰度在暴露于水溶性PM2.5提取物(WSPE)的A549细胞中发生了显著变化。其中,12个点上调,15个点下调。通过基质辅助激光解吸/电离飞行时间串联质谱和数据库搜索进一步鉴定了22种蛋白质。结果表明,氧化应激、代谢紊乱、信号转导失调、蛋白质合成与降解异常以及细胞骨架紊乱是导致WSPE介导的人肺细胞毒性的主要因素。进一步提出,通过p53、c-Myc和p21途径诱导细胞凋亡可能是WSPE应激下A549细胞发生的关键毒理学事件之一。此处获得的数据将有助于我们理解与PM2.5相关的毒性机制,并开发出指示可吸入PM2.5暴露的有用生物标志物。