College of Eco-Environmental Engineering, Qinghai University, Xining, 810016, China.
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, No. 521 Ningda Road, Chengbei District, Xining, 810016, China.
BMC Genomics. 2021 Jun 5;22(1):416. doi: 10.1186/s12864-021-07673-4.
Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni.
We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was "Ribosome" in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells.
Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.
铜在水产养殖中已使用多年，作为一种有效的杀藻剂或鱼类寄生虫治疗药物。它是生物体中具有许多功能的必需营养素，但在高浓度下具有毒性。然而，铜对鱼类的毒性仍不清楚。在这项研究中，我们以裸鲤为模型。使用来自不同组织（包括鳃、肾和肝）的 RNA-seq 数据，研究铜毒在裸鲤中的潜在机制。
我们比较了不同组织在不同时间铜离子处理后的转录组。经过 72 小时铜离子处理后，鳃和肝中差异表达基因的数量发生了显著变化，但肾中没有。在 KEGG 功能富集中，鳃和肝中差异表达基因的模式也相似。差异表达基因最富集的途径是“核糖体”。此外，我们使用 qPCR 和 RNA-seq 数据分析了氧化应激反应和蛋白质合成相关基因的表达水平。结果表明，在鳃和肝中，几个与氧化应激反应相关的基因均上调。这些基因的上调表明铜处理引起了氧化应激，这可能导致核糖体损伤。此外，结果表明，在肝脏中，转录延伸因子 Eef1b2 的表达在氧化应激下降低，翻译起始因子 Eif4ebp1、eIF2α 和延伸因子 eEF2 的表达上调。这些结果支持氧化应激抑制细胞内蛋白质合成的观点。
我们的结果表明，铜暴露在不同组织中引起了不同的反应，因为基因表达模式在鳃或肝中发生了很大变化，而对肾脏的影响相对较弱。此外，我们的结果表明，核糖体相关基因的表达模式，即细胞内协调蛋白质合成的复杂分子机器，以及翻译起始因子和延伸因子，在裸鲤的鳃和肝中都受到铜暴露的影响。这一结果使我们推测，下调全局蛋白质合成是鱼类对金属诱导的氧化应激的一种急性反应策略。此外，我们推测这种策略不仅存在于蛋白质的选择性翻译中，也存在于组织和细胞中功能蛋白的特异性翻译中。
