College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, PR China.
College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China.
Fish Shellfish Immunol. 2019 Oct;93:1093-1099. doi: 10.1016/j.fsi.2019.07.022. Epub 2019 Jul 13.
Chlorpyrifos (CPF) has become a mainly pollution in water environment. Micro-RNAs (miRNAs) play an important part in the development of apoptosis and autophagy. However, the potential mechanism of CPF induced kidney toxicity and the roles of miRNAs are still unclear. To explore the underlying mechanism, the kidney of common carp exposed to different concentrations of CPF for 40 days was used as a research object. We found that CPF could damage the ultrastructure and function of kidney; and also caused antioxidant system disorder. CPF inhibited the mRNA level of miR-19a which improved AMP-activated protein kinase (AMPK). Furthermore, the detection of apoptosis and autophagy relative genes showed that the expressions of TSC complex subunit 2 (TSC2), light chain 3 (LC3), Dynein, tumor protein 53 (p53), Bcl-2 associated X protein (Bax), caspase-3 and caspase-9 were enhanced and the expressions of nechanistic target of rapamycin (mTOR), Ras homolog mTORC1 binding (Rheb) and B-cell lymphoma (Bcl-2) were reduced in dose-dependent way. Taken together, we conclude that CPF causes oxidative stress and miR-19a-AMPK axis disorder, thereby promotes apoptosis and autophagy in common carp kidney. Our study will provide theoretical basis for toxicology research and environmental protection of CPF.
毒死蜱(CPF)已成为水环境中的主要污染物。微小 RNA(miRNA)在细胞凋亡和自噬的发展中起着重要作用。然而,CPF 诱导肾毒性的潜在机制和 miRNA 的作用尚不清楚。为了探讨其潜在机制,以暴露于不同浓度 CPF 40 天的鲤鱼肾脏为研究对象。结果发现 CPF 可损伤肾脏的超微结构和功能,并导致抗氧化系统紊乱。CPF 抑制 miR-19a 的 mRNA 水平,从而增强 AMP 激活的蛋白激酶(AMPK)。此外,对凋亡和自噬相关基因的检测表明,TSC 复合物亚基 2(TSC2)、轻链 3(LC3)、动力蛋白、肿瘤蛋白 53(p53)、Bcl-2 相关 X 蛋白(Bax)、半胱天冬酶-3 和半胱天冬酶-9 的表达增强,而雷帕霉素(mTOR)、Ras 同源物 mTORC1 结合(Rheb)和 B 细胞淋巴瘤(Bcl-2)的表达呈剂量依赖性降低。综上所述,CPF 引起氧化应激和 miR-19a-AMPK 轴紊乱,从而促进鲤鱼肾脏细胞凋亡和自噬。本研究为 CPF 的毒理学研究和环境保护提供了理论依据。