Metabolomics reveals disturbed metabolic pathways in human lung epithelial cells exposed to airborne fine particulate matter
Metabolomics reveals disturbed metabolic pathways in human lung epithelial cells exposed to airborne fine particulate matter
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代谢组学揭示暴露于空气中细颗粒物的人肺上皮细胞的代谢途径受到干扰
DOI：
10.1039/c5tx00003c
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Shen, Heqing
中科院分区：
文献类型：
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作者：
Huang, Qingyu;Zhang, Jie;Shen, Heqing
接触空气中的细颗粒物 (PM2.5) 与多种不良健康影响有关；然而，PM2.5引起的肺毒性的分子机制仍未得到很好的阐明。通过进行基于超高效液相色谱/质谱的代谢组学分析，本研究研究了暴露于 PM2.5 提取物的人肺上皮细胞 (A549) 代谢组的变化。研究发现不同的代谢组学特征与 PM2.5 治疗相关。 PM2.5以剂量依赖性方式显着改变了16种细胞内代谢物的丰度，其中13种减少，3种增加。通过通路分析发现，柠檬酸循环、氨基酸生物合成与代谢、谷胱甘肽代谢是PM2.5干扰A549细胞的主要代谢通路。此外，参与这些途径的几个关键基因的表达变化进一步验证了本文代谢组学观察到的代谢改变。有人认为，PM2.5 诱导的氧化应激可能会扰乱细胞线粒体中的代谢过程。总体而言，这些结果有助于增进对 PM2.5 相关毒理学机制的了解，并确定指示可吸入 PM2.5 暴露的潜在生物标志物。
Exposure to airborne fine particulate matter (PM2.5) has been associated with a variety of adverse health effects; however, the molecular mechanisms involved in PM2.5-elicited pulmonary toxicity are still not well elucidated. By conducting an ultra-high performance liquid chromatography/mass spectrometry-based metabolomics analysis, the present study investigated alterations of metabolome in human lung epithelial cells (A549) exposed to PM2.5 extracts. Distinct metabolomic profiles were found to be associated with PM2.5 treatment. PM2.5 significantly changed the abundance of 16 intracellular metabolites in a dose-dependent manner, of which 13 were decreased and three were increased. By pathway analysis, it was shown that the citrate cycle, amino acid biosynthesis and metabolism, and glutathione metabolism were the major metabolic pathways disturbed by PM2.5 in A549 cells. In addition, changes in expression of several key genes involved in these pathways further validated the metabolic alterations observed by metabolomics herein. It is suggested that PM2.5-induced oxidative stress may contribute to perturbation of metabolic processes occurring in cell mitochondria. Overall, these results aid in improving understanding of the toxicological mechanisms related to PM2.5, and identifying potential biomarkers indicative of inhalable PM2.5 exposure.