期刊
TOXICOLOGY
卷 477, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2022.153271
关键词
PM2.5; ROS; MAPKs; Autophagy; Apoptosis
资金
- NIH [ES023693, ES028911, HL147856, KSEF-148-RED-502 - 16-381]
- Kentucky Lung Cancer Research Program
- National Institute for Environmental Health Sciences [P30ES030283]
This study evaluated the toxic effects and mechanisms of fine airborne particulate matter (PM2.5) on human glioblastoma LN-229 cells. The results showed that PM2.5 exposure reduced cell viability and increased autophagy, apoptosis, and ROS production. Further experiments revealed that PM2.5-induced autophagy and apoptosis were mainly caused by ROS generation, particularly by mitochondria, and JNK activation.
Air pollution is a public health threat and global epidemiological studies have shown that ambient air pollutants are closely related to various poor health conditions, including neurodegenerative diseases. Here, we evaluated the toxic effects and the underlying mechanisms of fine airborne particulate matter (PM2.5) on human glioblastoma LN-229 cells. Our results showed that exposure of LN-229 cells to PM2.5 (>= 200 mu g/mL) significantly reduced cell viability. PM2.5 exposure increased autophagy, apoptosis, and ROS production in the cells. Pretreatment with a ROS scavenger, catalase, or depletion of mtDNA (rho(0) cells) abolished PM2.5-induced autophagy and apoptosis. PM2.5 exposure also activated MAPK signals in cells, which were blocked by catalase pretreatment or mtDNA depletion. Furthermore, inhibition of JNK, but not ERK1/2 or p38, attenuated PM2.5-induced autophagy and apoptosis in cells. Finally, suppression of autophagy with Bafilomycin Al or Beclin 1 siRNA exacerbated PM2.5-induced apoptosis, indicating a protective role of autophagy against PM2.5-induced apoptosis. Our results demonstrated that exposure of LN-229 cells to PM2.5 caused autophagy and apoptosis through PM2.5-induced ROS generation, mainly by mitochondria, and JNK activation. Autophagy may have a transient protective response in PM2.5-induced apoptosis. These findings have important implications for understanding the potential neurotoxicity of PM2.5.
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