代谢组学
代谢途径
细胞生物学
内质网
纳米毒理学
细胞毒性
自噬
氧化应激
细胞毒性T细胞
生物途径
线粒体
程序性细胞死亡
化学
生物
毒性
细胞凋亡
新陈代谢
生物化学
生物信息学
体外
基因
基因表达
有机化学
作者
Swee Ling Lim,Cheng Teng Ng,Li Zou,Yonghai Lu,Jiaqing Chen,Boon‐Huat Bay,Han‐Ming Shen,Choon Nam Ong
出处
期刊:Nanotoxicology
[Informa]
日期:2019-07-05
卷期号:13 (8): 1117-1132
被引量:159
标识
DOI:10.1080/17435390.2019.1640913
摘要
Engineered nanomaterials are of public health concern. Recently, there has been an increasing attention on the toxicity of nanoplastics and nanoZnO because of their increasing utilization and presence in the environment. However, knowledge of their toxicological behavior and metabolic interactions with the cellular machinery that determine their potential health effects are extremely limited. In this study, the cellular uptake, cytotoxic effects, and metabolic responses of bronchus epithelial (BEAS-2B) cells exposed to nanopolystyrene (nanoPS) and a widely used metallic nanoparticle, nanoZnO, were investigated using a tandem mass spectrometry-based metabolomics approach. The results revealed that even with low cytotoxicity, these nanoparticles (NPs) affected cell metabolism. NanoPS exposure showed autophagic- and endoplasmic reticulum (ER) stress-related metabolic changes such as increased in amino acids and tricarboxylic acid cycle (TCA) intermediate metabolites, a process known to play a critical role in regulating cell resistance to cytotoxic effects. Both metabolomics profiling and ER-stress pathway, together with quantitative real-time RT-polymerase chain reaction (qRT-PCR) analyses, demonstrated that autophagy was reciprocally regulated to couple metabolic and transcriptional reprograming. In contrast, nanoZnO-induced ROS-mediated cell death was associated with mitochondrial dysfunction and interference in regulating energy metabolism. Collectively, these two types of NPs were observed to cause perturbations albeit differential in cellular metabolism associated with their cytotoxic effects. Our findings provided an in depth understanding of metabolic changes influenced by two different types of NPs, with contrasting molecular mechanisms for the adverse effects observed.
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