【摘 要】
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OBJECTIVE The increasing of human exposure to silica nanoparticles (SNPs) makes it urgent for in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological sys
【机 构】
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School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory o
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OBJECTIVE The increasing of human exposure to silica nanoparticles (SNPs) makes it urgent for in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological systems.Autophagic cell death is recognized as an alternative cell death pathway, yet there have been scarcely research of SNPs on the autophagic cell death and its associated mechanism.METHODS In the present study, we characterized the cellular uptake of the SNPs and further verified the activation of autophagy by MDC-staining of autophagic vacuoles, LC3-Ⅰ/LC3-Ⅱ conversion and TEM ultrastructural observation.Autophagic cell death was evaluated by the cellular co-staining assay.The underlying mechanisms of SNPs-induced autophagy and autophagic cell death were investigated by the intracellular ROS detection, autophagy inhibitor 3-MA and ROS scavenger NAC.RESULTS The results showed that all the MDC-positive cells, fluorescence intensity and LC3-Ⅱ protein level were gradually increased as the elevated concentrations of the SNPs.The typically morphological characteristics at different stage of autophagy development were observed (autophagosomes and autolysosomes).In addition, the double-stained cells were determined to be cell death by autophagy.The increasing cellular ROS level was correlated with the increase of autophagy activation and both the inhibitors of 3-MA and NAC were effectively suppressed the SNPs-induced autophagy and cell death.CONCLUSION For the first time, we reported a novel mode of action (MOA) for the SNPs involving dose-dependent autophagy induction and ultimate autophagic cell death resulting from the ROS generation in HepG2 cells.This study provides a new potential pathway of the SNPs-induced cell death and suggests the urgent need for safety evaluation of the SNPs before their utilization.
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