College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People's Republic of China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, People's Republic of China.
J Hazard Mater. 2022 Feb 15;424(Pt A):127318. doi: 10.1016/j.jhazmat.2021.127318. Epub 2021 Sep 24.
Chlorpyrifos (CPF), a widely used organophosphorus pesticide has caused water pollution, threatening aquatic organisms. MicroRNAs (miRNAs) highly conserved noncoding RNAs, that regulate various cell death processes, including pyroptosis. To investigate the effect of CPF exposure on epithelioma papulosum cyprini (EPC) cell pyroptosis and the role of the miR-124-3p/CAPN1 axis, we established miR-124 overexpression and inhibition EPC cell models of CPF exposure. The target of the miR-124-3p/CAPN1 axis was primarily confirmed by the double luciferase reporter assay. Pyroptosis was demonstrated to occur in CPF-exposed EPC cells and was accompanied by mitochondrial membrane potential depletion, ROS level elevation and pyroptotic indicator expression upregulation. PD150606 was supplied as a CAPN1 inhibitor, alleviating CPF-induced mitochondrial dysfunction, and alleviating the increased expression of NLRP3, CASP1, IL1β and GSDMD. In conclusion, CPF induces pyroptosis by regulating the miR-124-3p/CAPN1 axis. This study enriches the cytotoxicity study of CPF, and provides new theoretical fundamentals for exploration of miRNA and its target protein response to water contaminants.
毒死蜱（CPF）是一种广泛使用的有机磷农药，已造成水污染，威胁水生生物。microRNAs（miRNAs）是高度保守的非编码 RNA，调节包括细胞焦亡在内的多种细胞死亡过程。为了研究 CPF 暴露对鲤鱼上皮瘤细胞（EPC）细胞焦亡的影响及其 miR-124-3p/CAPN1 轴的作用，我们建立了 miR-124 过表达和抑制 CPF 暴露的 EPC 细胞模型。miR-124-3p/CAPN1 轴的靶标主要通过双荧光素酶报告基因检测来确认。CPF 暴露的 EPC 细胞发生细胞焦亡，伴有线粒体膜电位耗竭、ROS 水平升高和焦亡标志物表达上调。PD150606 作为 CAPN1 抑制剂，可减轻 CPF 诱导的线粒体功能障碍，并减轻 NLRP3、CASP1、IL1β 和 GSDMD 的表达增加。总之，CPF 通过调节 miR-124-3p/CAPN1 轴诱导细胞焦亡。本研究丰富了 CPF 的细胞毒性研究，为探索 miRNA 及其靶蛋白对水污染物的反应提供了新的理论基础。
