Yang Peiyan, Ke Sunkui, Tu Li, Wang Yange, Ye Shefang, Kou Shengbin, Ren Lei
Surgical Institute, First Affiliated Hospital of Xiamen University, Xiamen 361004, P. R. China.
Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, Xiamen 361004, P. R. China.
ACS Biomater Sci Eng. 2020 Mar 9;6(3):1764-1775. doi: 10.1021/acsbiomaterials.9b01932. Epub 2020 Feb 24.
Molybdenum disulfide quantum dots (MoS QDs) represent an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenide nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of the inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS QD-induced pyroptosis. Additionally, MoS QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavengers could diminish the MoS QD-mediated NLRP3 inflammasome activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS QD exposure in microglial cells, affording novel insights into the neurotoxicity of MoS QDs and facilitating the rational design and application of functional MoS QDs in neuroscience.
二硫化钼量子点（MoS QDs）是一类新兴的二维（2D）原子层状过渡金属二硫属化物纳米结构，其横向尺寸仅为几纳米，作为用于各种神经系统疾病诊疗应用的多功能平台显示出诱人的潜力。然而，MoS QDs对小胶质细胞的潜在影响仍不清楚。在本报告中，我们表明，小胶质细胞暴露于MoS QDs会触发NLRP3炎性小体激活，这可通过半胱天冬酶-1的无活性前体裂解为其活性形式以及下游促炎细胞因子释放增加来揭示，导致小胶质细胞通过半胱天冬酶-1依赖性细胞焦亡而死亡。我们还发现MoS QDs激活了自噬，并且用特异性抑制剂抑制自噬会增强MoS QD诱导的细胞焦亡。此外，MoS QDs刺激BV-2细胞中线粒体衍生的活性氧（mtROS）生成。然而，活性氧清除剂可减少MoS QD介导的小胶质细胞中NLRP3炎性小体激活和细胞焦亡性细胞死亡。总体而言，我们的研究结果确定细胞焦亡是小胶质细胞对MoS QD暴露的细胞反应，为MoS QDs的神经毒性提供了新的见解，并促进了功能性MoS QDs在神经科学中的合理设计和应用。
