Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 510632, China.
Department of Ultrasound, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Ecotoxicol Environ Saf. 2021 Jul 1;217:112245. doi: 10.1016/j.ecoenv.2021.112245. Epub 2021 Apr 21.
Paraquat (PQ) is a non-selective herbicide with strong toxicity to humans and mammals. However, the proteome regulation of cells by PQ is still unclear, limiting the development of effective antidotes. Studies have shown that a slight excess of intracellular copper levels could be beneficial to the survival under exposure to PQ. In this study, Saccharomyces cerevisiae was used as a model to explore the regulation effect of copper ions on PQ poisoning by the approach of date independent acquisition proteomics. The results showed that toxic effect of PQ was primarily induced by oxidative damage in the mitochondria and the disorder of gene expression. The addition of Cu involved a series of favorable reactions to cell survival under PQ stress, including activation of the mitogen-activated protein kinase signaling pathway, regulation of processes such as sulfur metabolism, carbon metabolism and gene expression in cells. The generation of glutathione, heme and steroids advantageous to cell growth under stress was also increased. These findings inferred that therapeutic concentration of copper ions could prolong the survival of cells under PQ stress.
百草枯（PQ）是一种对人类和哺乳动物具有很强毒性的非选择性除草剂。然而，PQ 对细胞的蛋白质组调节仍不清楚，这限制了有效解毒剂的开发。研究表明，细胞内铜水平略有过剩可能有助于在暴露于 PQ 下的生存。在这项研究中，使用酿酒酵母作为模型，通过无依赖日期采集蛋白质组学的方法探索铜离子对 PQ 中毒的调节作用。结果表明，PQ 的毒性作用主要是由线粒体中的氧化损伤和基因表达紊乱引起的。Cu 的添加涉及一系列有利于细胞在 PQ 应激下存活的有利反应，包括丝裂原激活蛋白激酶信号通路的激活，以及细胞中硫代谢、碳代谢和基因表达等过程的调节。应激下有利于细胞生长的谷胱甘肽、血红素和甾体的产生也增加了。这些发现推断治疗浓度的铜离子可以延长细胞在 PQ 应激下的存活时间。
