期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 170, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.113469
关键词
AgNPs; Neuroinflammation; Autophagy; Lysosome; Autophagosome -lysosome fusion
资金
- National Natural Science Foundation of China
- Postgraduate Research & Practice Innova-tion Program of Jiangsu Province
- [82273674]
- [81573186]
- [21876026]
- [KYCX21_0165]
- [KYCX20_0152]
This study evaluated the effects of silver nanoparticles (AgNPs) on different stages of autophagy and found that they induced neuroinflammation and blocked autophagic flux. AgNPs hindered autophagic flux by inhibiting the fusion between autophagosomes and lysosomes, aggravating the neurotoxicity caused by AgNPs.
Silver nanoparticles (AgNPs) have been incorporated in many consumer and biomedical products. Serious concerns have been expressed about the environmental and public health risks caused by nanoparticles. In previous studies, we found that AgNPs induced microglia polarization of the inflammatory phenotype. Autophagy was a critical for AgNPs-induced neuroinflammation. In the present study, we evaluated in detail the effects of AgNPs in different stages of the autophagy process, and we found that AgNPs induced neuroinflammatory responses and autophagic flux blockage both in the mouse brain and BV2 cells. AgNPs inhibited autophagosome-lysosome fusion and impaired the lysosomal functions by reducing the levels of lysosomalassociated membrane proteins, promoting lysosome membrane permeability and altering the lysosomal acidic microenvironment. These changes resulted in the defects in autophagic substrate clearance and subsequently led neuroinflammation. In addition, the elevation of autophagy could prevent the neuroinflammation induced by AgNPs. As a result, AgNPs hindered autophagic flux by inhibiting autophagosome fusion with lysosomes, thus aggravating the AgNPs-induced neurotoxicity. These findings will provide new insights to investigate the molecular mechanisms of neurotoxicity caused by AgNPs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据