Zhang Mei, Wang Ying, Wong Ricky M S, Yung Ken Kin Lam, Li Ruijin
Institute of Environmental Science, Shanxi University, Taiyuan, PR China.
Institute of Environmental Science, Shanxi University, Taiyuan, PR China; Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
Neurotoxicology. 2022 Jan;88:187-195. doi: 10.1016/j.neuro.2021.11.012. Epub 2021 Nov 20.
Exposure to ambient fine particulate matter (PM) may contribute to brain injury, however, the molecular mechanisms have not yet been fully described. In this study, the human SH-SY5Y cells were treated with PM with different concentrations (0, 25, 100, and 250 μg/mL) for 24 h to investigate the cell apoptosis mediated by endoplasmic reticulum (ER) stress. The ratio of apoptosis, Ca level, biomarkers of ER stress and apoptosis were determined. The results revealed that PM triggered the increase of apoptosis ratio and cellular Ca levels. Compared with control, the expression of GRP78 and phosphorylation of IER1α and p38 were enhanced significantly in the cells under the conditions of PM exposure for activating ER stress signals. Besides, the key genes (CHOP/DR5/Caspase8/Caspase12) in ER stress-induced apoptosis signals were up-regulated after the PM treatment compared to the control. The results suggested PM induced apoptosis in SH-SY5Y cells by the stimulation of ER stress, which may be the potential mechanism of neurological diseases incurred by PM.
暴露于环境细颗粒物（PM）可能会导致脑损伤，然而，其分子机制尚未完全阐明。在本研究中，将人SH-SY5Y细胞用不同浓度（0、25、100和250μg/mL）的PM处理24小时，以研究内质网（ER）应激介导的细胞凋亡。测定了凋亡率、钙水平、ER应激和凋亡的生物标志物。结果显示，PM引发了凋亡率和细胞钙水平的升高。与对照组相比，在PM暴露条件下的细胞中，GRP78的表达以及IRE1α和p38的磷酸化显著增强，以激活ER应激信号。此外，与对照组相比，PM处理后ER应激诱导的凋亡信号中的关键基因（CHOP/DR5/Caspase8/Caspase12）上调。结果表明，PM通过刺激ER应激诱导SH-SY5Y细胞凋亡，这可能是PM引发神经疾病的潜在机制。
