Toxicological effects of tris(1,3-dichloro-2-propyl) phosphate in oyster Crassostrea gigas using proteomic and phosphoproteomic analyses
Toxicological effects of tris(1,3-dichloro-2-propyl) phosphate in oyster Crassostrea gigas using proteomic and phosphoproteomic analyses
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DOI：
10.1016/j.jhazmat.2022.128824
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发表时间：
2022-07-15
影响因子：
13.6
通讯作者：
Wu，Huifeng
中科院分区：
文献类型：
--
作者：
Yin，Chengcheng;Sun，Zuodeng;Wu，Huifeng
磷酸三（1，3-二氯-2-丙基）酯（TDCIPP）是一种典型的有机磷污染物，在水环境中广泛存在。研究表明，蛋白质磷酸化可能是TDCIPP发挥多种毒性作用的重要途径。然而，缺乏高通量的调查如何TDCIPP影响蛋白质磷酸化。本研究采用蛋白质组学和磷酸化蛋白质组学技术，结合传统方法，研究了0.5、5和50 μg/L TDCIPP对牡蛎的毒性效应。整合组学分析显示，TDCIPP失调转录，能量代谢，细胞凋亡和细胞增殖，无论是直接磷酸化的关键蛋白或磷酸化其上游信号通路。乙酰胆碱酯酶活性的U形反应表明TDCIPP以兴奋效应方式具有神经毒性。此外，caspase-9活性的增加以及真核细胞翻译起始因子4 E、细胞分裂控制蛋白42和转化生长因子-β1诱导蛋白的表达或磷酸化水平的改变，表明细胞凋亡和增殖之间的稳态被破坏，这与消化细胞脱落的观察结果相一致。总之，结合蛋白质组学和磷酸化蛋白质组学分析显示出识别分子事件的能力，这为TDCIPP的毒理学机制提供了新的见解。
As a typical organophosphorus pollutant, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been widely detected in aquatic environment. Previous studies showed that protein phosphorylation might be a vital way of TDCIPP to exert multiple toxic effects. However, there is a lack of high-throughput investigations on how TDCIPP affected protein phosphorylation. In this study, the toxicological effects of TDCIPP were explored by proteomic and phosphoproteomic analyses together with traditional means in oystersCrassostrea gigastreated with 0.5, 5 and 50 μg/L TDCIPP for 28 days. Integration of omic analyses revealed that TDCIPP dysregulated transcription, energy metabolism, and apoptosis and cell proliferation by either directly phosphorylating pivotal proteins or phosphorylating their upstream signaling pathways. The U-shaped response of acetylcholinesterase activities suggested the neurotoxicity of TDCIPP in a hormesis manner. What’s more, the increase in caspase-9 activity as well as the expression or phosphorylation alterations in eukaryotic translation initiation factor 4E, cell division control protein 42 and transforming growth factor-β1-induced protein indicated the disruption of homeostasis between apoptosis and cell proliferation, which was consistent with the observation of shedding of digestive cells. Overall, combination of proteomic and phosphoproteomic analyses showed the capability of identifying molecular events, which provided new insights into the toxicological mechanisms of TDCIPP.