Transcriptome analysis of different sizes of 3-mercaptopropionic acid-modified cadmium telluride quantum dot-induced toxic effects reveals immune response in rat hippocampus

Transcriptome analysis of different sizes of 3-mercaptopropionic acid-modified cadmium telluride quantum dot-induced toxic effects reveals immune response in rat hippocampus
复制标题

不同大小的3-巯基丙酸修饰的碲化镉量子点诱导的毒性作用的转录组分析揭示了大鼠海马的免疫反应

DOI:
10.1002/jat.3629
复制
发表时间:
2018-09-01
影响因子:
3.3
通讯作者:
Tang, Meng
Tang, Meng
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Tianshu;Liang, Xue;Tang, Meng

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近年来,越来越多的含镉量子点(QDs)的生物安全性研究表明,QDs可能对生物体的中枢神经系统(CNS)产生不良影响,但其作用机制尚未见报道。本研究采用全转录组测序技术分析了两种尺寸的碲化镉(CdTe)量子点处理后大鼠海马全基因组基因表达谱的变化,以更好地了解CdTe量子点引起中枢神经系统毒性作用的机制。我们确定了2095差异表达基因(DEG)。55个DEG介于对照和2.2 nm CdTe量子点之间,1180个介于对照和3.5 nm CdTe量子点之间,860个介于两种CdTe量子点之间。在转录组水平上,3.5 nm CdTe QD暴露可能比2.2 nm CdTe QD在大鼠海马中引起更严重的影响。经过生物信息学分析,我们发现大部分DEG丰富的基因本体论亚类和京都基因和基因组百科全书途径与免疫系统过程相关。例如,Gene Ontology子类别包括免疫反应、炎症反应和T细胞增殖;京都基因和基因组百科全书通路包括NOD/Toll样受体信号通路、核因子-B信号通路、肿瘤坏死因子信号通路、自然杀伤细胞介导的细胞毒性和T/B细胞受体信号通路。传统的毒理学实验证实了CdTe量子点暴露大鼠的全身免疫反应和中枢神经系统炎症。该转录组分析不仅揭示了CdTe量子点致神经毒性的可能分子机制,也为相关研究提供了参考。
Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS. We identified 2095 differentially expressed genes (DEGs). Fifty-five DEGs were between the control and 2.2 nm CdTe QDs, 1180 were between the control and 3.5 nm CdTe QDs and 860 were between the two kinds of CdTe QDs. It seemed that the 3.5 nm CdTe QD exposure might elicit severe effects in the rat hippocampus than 2.2 nm CdTe QDs at the transcriptome level. After bioinformatics analysis, we found that most DEG-enriched Gene Ontology subcategories and Kyoto Encyclopedia of Genes and Genomes pathways were related with the immune system process. For example, the Gene Ontology subcategories included immune response, inflammatory response and T-cell proliferation; Kyoto Encyclopedia of Genes and Genomes pathways included NOD/Toll-like receptor signaling pathway, nuclear factor-B signaling pathway, tumor necrosis factor signaling pathway, natural killer cell-mediated cytotoxicity and T/B-cell receptor signaling pathway. The traditional toxicological examinations confirmed the systemic immune response and CNS inflammation in rats exposed to CdTe QDs. This transcriptome analysis not only revealed the probably molecular mechanisms of CdTe QDs causing neurotoxicity, but also provided references for the further related studies.