Feng Lin, Yang Xiaozhe, Asweto Collins Otieno, Wu Jing, Zhang Yannan, Hu Hejing, Shi Yanfeng, Duan Junchao, Sun Zhiwei
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, People's Republic of China.
Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, People's Republic of China.
Environ Sci Pollut Res Int. 2017 Apr;24(12):11683-11693. doi: 10.1007/s11356-017-8773-3. Epub 2017 Mar 22.
Air pollution has been a major environment-related health threat. Most of the studies on PM toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells. GO analysis showed that cellular processes such as immune response, cell maturation, embryonic heart tube morphogenesis, cellular response to electrical stimulus, skeletal muscle tissue regeneration, and negative regulation of signal transduction were upregulated, while regulation of transcription (DNA-dependent), rhythmic process, protein destabilization apoptotic process, and innate immune response were downregulated. The pathway analysis indicates that cell signaling pathways such as cytokine-cytokine receptor interaction, NF-κB signaling pathway, chemokine signaling pathway, endocrine and other factor-regulated calcium reabsorption, HTLV-I infection, and cell adhesion molecules (CAMs) were upregulated, while the TGF-β signaling pathway was downregulated. In addition, Signal-net showed that the TUBA4A, ADRBK2, BRIX1, SMC4, EIF5B, PRMT1, ATG4B, and NDC80 genes were significantly decreased, while the expression of the KRT6B gene was markedly increased compared with the control group. All the genes were verified by qRT-PCR. This study had provided new bioinformatics evidences in PM-induced myocardial tissue toxicity which is necessary for further cardiovascular system toxicity studies.
空气污染一直是与环境相关的主要健康威胁。大多数关于细颗粒物（PM）毒性的研究都已在心血管系统和内皮细胞上得到验证。然而，关于PM诱导的心肌相关毒性的研究却很有限。本研究旨在全面了解PM对人心肌细胞（AC16）的毒性作用，并基于微阵列分析和生物信息学分析探索其分子机制。微阵列数据分析表明，与对照组相比，PM诱导的毒性影响了472个基因的表达，其中在人心肌（AC16）细胞中有166个基因上调，306个基因下调。基因本体（GO）分析显示，免疫反应、细胞成熟、胚胎心脏管形态发生、细胞对电刺激的反应、骨骼肌组织再生以及信号转导的负调控等细胞过程上调，而转录（DNA依赖性）调控、节律过程、蛋白质不稳定凋亡过程和固有免疫反应则下调。通路分析表明，细胞因子-细胞因子受体相互作用、核因子κB（NF-κB）信号通路、趋化因子信号通路、内分泌和其他因子调节的钙重吸收、人嗜T淋巴细胞Ⅰ型病毒（HTLV-I）感染以及细胞黏附分子（CAMs）等细胞信号通路上调，而转化生长因子-β（TGF-β）信号通路下调。此外，信号网络显示，与对照组相比，微管蛋白α4A（TUBA4A）、肾上腺素能受体结合激酶2（ADRBK2）、BRIX1蛋白、染色体结构维持蛋白4（SMC4）、真核翻译起始因子5B（EIF5B）、蛋白质精氨酸甲基转移酶1（PRMT1）、自噬相关蛋白4B（ATG4B）和核分裂纺锤体极体蛋白80（NDC80）基因显著降低，而角蛋白6B（KRT6B）基因的表达则明显增加。所有基因均通过实时定量聚合酶链反应（qRT-PCR）进行了验证。本研究为PM诱导心肌组织毒性提供了新的生物信息学证据，这对于进一步的心血管系统毒性研究是必要的。
