Cobbina Samuel Jerry, Mao Guanghua, Zhao Ting, Xu Hai, Zhang Zhen, Liu Hongyang, Zou Yanmin, Wu Xiangyang, Yang Liuqing
School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China.
School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, China.
Arch Environ Contam Toxicol. 2017 Apr;72(3):418-427. doi: 10.1007/s00244-016-0352-y. Epub 2017 Mar 2.
Currently, there is limited information on the toxicity of low concentration of metal mixtures in the environment. Of particular interest is the effect of low levels of metal mixtures on neurodevelopment of aquatic organisms. This study reports the neurological gene expressions after exposing zebrafish embryos to low concentration toxic heavy metals, 120 h post fertilization (hpf). Embryos were exposed to low concentration individual and mixtures of lead (Pb), mercury (Hg), arsenic (As), and cadmium (Cd). Quantitative real-time PCR was used to assess gene expressions. The findings of this study confirmed that exposure to low concentration heavy metals upregulated N-methyl-D-aspartate (NMDA) receptor subunits NMDAR2A (NR2A), NMDAR2B (NR2B), and NMDAR2D (NR2D) and B cell lymphoma (Bcl-2) genes. NR2A genes were significantly upregulated by 90 and 74%, respectively, on exposure to Pb + As and Pb + Cd. NR2B genes were upregulated by 85.3, 68.6, 62.7, and 62.7% on exposure to As, Pb + Hg, Pb + As, and Pb + Cd, respectively. Exposure to As, Pb + Cd, and Pb + Hg + As significantly upregulated Bcl-2 genes by 2.01-, 1.84-, and 1.80-fold, respectively. NR1A and C-fos gene expressions were not significantly different from control. Upregulation of NMDAR subunits and Bcl-2 genes in this study was largely a counter measure against insults from exposure to low concentration heavy metals. Principal component analysis confirmed the influence of low concentration individual and mixtures of Pb, Hg, As, and Cd on gene expression of NMDAR subunits and Bcl-2. These data suggest that altered expression of NMDA receptor subunits and Bcl-2 genes may explain toxicity of low concentration individual and mixtures of Pb, Hg, As, and Cd.
目前，关于环境中低浓度金属混合物的毒性信息有限。特别值得关注的是低水平金属混合物对水生生物神经发育的影响。本研究报告了受精后120小时（hpf）将斑马鱼胚胎暴露于低浓度有毒重金属后神经基因的表达情况。胚胎暴露于低浓度的铅（Pb）、汞（Hg）、砷（As）和镉（Cd）的单一物质及其混合物中。采用定量实时PCR来评估基因表达。本研究结果证实，暴露于低浓度重金属会使N-甲基-D-天冬氨酸（NMDA）受体亚基NMDAR2A（NR2A）、NMDAR2B（NR2B）和NMDAR2D（NR2D）以及B细胞淋巴瘤（Bcl-2）基因上调。暴露于Pb + As和Pb + Cd时，NR2A基因分别显著上调90%和74%。暴露于As、Pb + Hg、Pb + As和Pb + Cd时，NR2B基因分别上调85.3%、68.6%、62.7%和62.7%。暴露于As、Pb + Cd和Pb + Hg + As时，Bcl-2基因分别显著上调2.01倍、1.84倍和1.80倍。NR1A和C-fos基因表达与对照组无显著差异。本研究中NMDAR亚基和Bcl-2基因的上调在很大程度上是对暴露于低浓度重金属所致损伤的一种应对措施。主成分分析证实了低浓度的Pb、Hg、As和Cd单一物质及其混合物对NMDAR亚基和Bcl-2基因表达的影响。这些数据表明，NMDA受体亚基和Bcl-2基因表达的改变可能解释了低浓度的Pb、Hg、As和Cd单一物质及其混合物的毒性。
