Duan Shuyin, Zhang Meihua, Sun Yaqiong, Fang Zhenya, Wang Hefeng, Li Shuxian, Peng Yanze, Li Juan, Li Junxia, Tian Jiaqi, Yin Haoyu, Yao Sanqiao, Zhang Lin
Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan 250001, China; Department of Occupational and Environmental Hygiene, School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan 250001, China.
J Hazard Mater. 2020 Sep 5;396:122747. doi: 10.1016/j.jhazmat.2020.122747. Epub 2020 Apr 18.
Exposure to PM has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ± 69 μg/m, PM was rich in heavy metals and organic pollutants. After exposure to PM, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.
接触细颗粒物（PM）与呼吸系统疾病有关，但对其分子机制的了解有限。在此，对中国中部地区的PM进行了监测和收集，并研究了其对人支气管上皮细胞（BEAS-2B）的细胞毒性机制。PM的平均浓度为109±69μg/m，富含重金属和有机污染物。暴露于PM后，BEAS-2B细胞的活力下降，预计有510个失调基因通过氧化磷酸化信号通路抑制ATP合成来诱导坏死性凋亡。细胞实验表明，ATP含量下调，而坏死性凋亡指标RIP3的表达上调。此外，负责ATP合成的四种酶，包括ATP5F、NDUF、COX7A和UQCR下调，而负责坏死性凋亡的RELA和CAPN1两个基因上调。此外，应用N-乙酰半胱氨酸作为ATP合成的增强剂，可逆转ATP5F、NDUF和COX7A的下调，从而减轻RELA、CAPN1和RIP3的升高。总之，暴露于PM会下调ATP5F、NDUF、COX7A和UQCR，通过氧化磷酸化信号通路抑制ATP合成，随后上调RELA和CAPN1，最终导致BEAS-2B细胞坏死性凋亡。
