文献类型：期刊文献

英文题名：Pyraclostrobin induced AMPK/mTOR pathways mediated autophagy in RAW264.7 macrophages

作者：Han, Shuang[1];Lu, Jian[1];Gao, Jufang[2];Cheng, Jiagao[1];Xu, Wenping[1];Tao, Liming[1];Zhang, Yang[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, 130 Meilong Rd, Shanghai, Peoples R China;[2]Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai, Peoples R China

年份：2021

卷号：56

期号：9

起止页码：793

外文期刊名：JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES

收录：;EI(收录号：20213210731916);WOS:【SCI-EXPANDED(收录号:WOS:000681276300001)】；

基金：This work was financial supported by Shanghai Sailing Program (NO.19YF1411100) and Innovation Program of Shanghai Municipal Education Commission, China (NO. 201701070002E00037) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Strobilurin fungicides; pyraclostrobin; cytotoxicity; autophagy; mammalian safety

摘要：Pyraclostrobin(PCT) is a highly effective and broad-spectrum strobilurin fungicide. The mode action of PCT is inhibiting mitochondrial respiration. With the widespread use of PCT in preventing and controlling crop diseases, its potential safety risks to mammals have gradually attracted attention. This paper focuses on the cytotoxicity of PCT and its molecular mechanism, RAW264.7 macrophages were selected as a research model and conducted systematic toxicology studies in vitro, including MTT assay, colony formation assay, alkaline comet assay, fluorescent staining, ATP assay and Western blotting. The results revealed that PCT decreased viability and inhibited the proliferation of RAW264.7 cells in a concentration- dependent manner. Interestingly, PCT induced DNA damage, the resulting autophagosome, the accumulation of Beclin-1, the reduction of p62, the translocation and the formation of LC3-II. Furthermore, the results showed that PCT-induced the production of excessive ROS, leading to mitochondrial permeability transition pore (mPTP) opening, ATP depletion, and the elimination of mitochondria by autophagy. Furthermore, PCT treatment group significantly enhanced the phosphorylation level of AMPK, decreased the mTOR and p70s6k phosphorylation levels and activated the AMPK/mTOR signaling pathway in RAW264.7 cells. In conclusion, these results showed that PCT induced autophagy in the RAW264.7 cells might potentially have risks to mammal safety.