Zhang Yu, Yang Dan, Yang Biao, Li Bingyu, Guo Jie, Xiao Chunling
Key Lab of Environmental Pollution and Microecology of Liaoning Province, Shenyang, Liaoning 110034, P.R. China.
Department of Pharmacology, Shenyang Medical College, Shenyang, Liaoning 110034, P.R. China.
Exp Ther Med. 2019 Jun;17(6):4371-4378. doi: 10.3892/etm.2019.7466. Epub 2019 Apr 3.
Fine particulate matter (PM2.5) pollution has become a serious problem in China. This study aims to elucidate the toxicity mechanism of PM2.5. Protein levels were detected by western blotting and RT-qPCR, and cell cycle was detected by flow cytometry. The results showed that exposure to PM2.5 induces cell cycle arrest and downregulation of the expression of cyclin D1 protein. Moreover, the protein expression of thymidylate synthase (TS) enzyme was found to be downregulated and the mRNA expression of TS was upregulated after PM2.5 exposure. Knockout of TS gene promoted cell cycle arrest and downregulation of the expression of cyclin D1 protein after PM2.5 exposure. Our data further revealed that PM2.5 exposure downregulates the expression of TS and cyclin D1 partially through the downregulation of the mammalian target of rapamycin (mTOR)/P70S6K1 signaling pathway. Thus, these findings indicate that PM2.5-induced cell cycle arrest might be due to the downregulation of mTOR/P70S6K1 signaling pathway, and thus inhibits the expression of TS protein.
细颗粒物(PM2.5)污染已成为中国的一个严重问题。本研究旨在阐明PM2.5的毒性机制。通过蛋白质印迹法和RT-qPCR检测蛋白质水平,通过流式细胞术检测细胞周期。结果表明,暴露于PM2.5会诱导细胞周期停滞,并下调细胞周期蛋白D1的表达。此外,发现胸苷酸合成酶(TS)的蛋白质表达下调,且PM2.5暴露后TS的mRNA表达上调。敲除TS基因会促进细胞周期停滞,并下调PM2.5暴露后细胞周期蛋白D1的表达。我们的数据进一步表明,PM2.5暴露通过下调雷帕霉素靶蛋白(mTOR)/P70S6K1信号通路,部分下调了TS和细胞周期蛋白D1的表达。因此,这些发现表明,PM2.5诱导的细胞周期停滞可能是由于mTOR/P70S6K1信号通路的下调,从而抑制了TS蛋白的表达。