Laboratory of Functional and Structural Biology, Institute of Biological Science, Federal University of Pará, Belém, Brazil.
Laboratory of Tissue Culture and Cytogenetics, Environmental Section, Evandro Chagas Institute, Ananindeua, Brazil.
Biol Trace Elem Res. 2023 Mar;201(3):1151-1162. doi: 10.1007/s12011-022-03225-3. Epub 2022 Apr 5.
The central nervous system is the main target of MeHg toxicity and glial cells are the first line of defense; however, their true role remains unclear. This study aimed to identify the global map of human glial-like (U87) cells transcriptome after exposure to a non-toxic and non-lethal MeHg concentration and to investigate the related molecular changes. U87 cells were exposed upon 0.1, 0.5, and 1 µM MeHg for 4 and 24 h. Although no changes were observed in the percentage of viable cells, the metabolic viability was significantly decreased after exposure to 1 µM MeHg for 24 h; thus, the non-toxic concentration of 0.1 µM MeHg was chosen to perform microarray analysis. Significant changes in U87 cells transcriptome were observed only after 24 h. The expression of 392 genes was down regulated while 431 genes were up-regulated. Gene ontology showed alterations in biological processes (75%), cellular components (21%), and molecular functions (4%). The main pathways showed by KEGG and Reactome were cell cycle regulation and Rho GTPase signaling. The complex mechanism of U87 cells response against MeHg exposure indicates that even a low and non-toxic concentration is able to alter the gene expression profile.
中枢神经系统是甲基汞毒性的主要靶标,神经胶质细胞是第一道防线;然而,它们的真正作用仍不清楚。本研究旨在确定人神经胶质样(U87)细胞在暴露于非毒性和非致死性甲基汞浓度后的转录组的全球图谱,并研究相关的分子变化。U87 细胞在 0.1、0.5 和 1µM 甲基汞下暴露 4 和 24 小时。尽管活细胞的百分比没有变化,但暴露于 1µM 甲基汞 24 小时后代谢活力显著降低;因此,选择非毒性浓度 0.1µM 甲基汞进行微阵列分析。仅在 24 小时后观察到 U87 细胞转录组的显着变化。392 个基因的表达下调,而 431 个基因上调。基因本体显示生物过程(75%)、细胞成分(21%)和分子功能(4%)的改变。KEGG 和 Reactome 显示的主要途径是细胞周期调控和Rho GTPase 信号。U87 细胞对甲基汞暴露的复杂反应机制表明,即使是低浓度和非毒性浓度也能够改变基因表达谱。