Autophagic effects and mechanisms of silver nanoparticles in renal cells under low dose exposure
Autophagic effects and mechanisms of silver nanoparticles in renal cells under low dose exposure
复制标题
低剂量暴露下纳米银对肾细胞的自噬作用及机制
DOI：
10.1016/j.ecoenv.2018.09.070
复制
发表时间：
2018-12-30
影响因子：
6.8
通讯作者：
Zhang, Zhihong
中科院分区：
文献类型：
--
作者：
Chen, Yue;Wang, Meng;Zhang, Zhihong
随着纳米技术的进步和独特的性能，银纳米粒子（AgNPs）在我们的工作和生活中得到了广泛的应用。然而，对纳米安全的关注尚未得到彻底理解。虽然越来越多的研究已经证明了AgNP在毒性剂量下介导的自噬，但很少有研究揭示AgNP在无毒浓度下诱导自噬的机制。在这里，我们研究了AgNPs介导的生物学效应对肾细胞自噬亚致死暴露。亚致死浓度的AgNPs可诱导HEK 293 T和A498细胞LC 3 II水平升高，自噬相关基因表达增加，表明AgNPs在较低浓度下可激活自噬。机制研究表明AMPK-mTOR信号参与了AgNP诱导的自噬过程，而PI 3 K/AKT/mTOR信号不参与自噬过程。此外，P62在AgNP处理的细胞中以不依赖于mTOR的方式升高。我们进一步发现，亚致死AgNPs暴露损害了溶酶体的完整性和蛋白酶活性。总之，我们的研究结果揭示了AgNPs在亚致死浓度下诱导肾细胞自噬的机制。
With the advancement of nanotechnology and unique properties, silver nanoparticles (AgNPs) have been generally used in our work and life. However, the concerns on nanosafety have not been thoroughly understood. Although mounting studies have documented AgNPs-mediated autophagy under toxic dose, very few studies have been made to reveal the mechanisms of AgNPs-induced autophagy at non-toxic concentrations. Here, we investigated AgNPs-mediated biological effects on autophagy in renal cells under sublethal exposure. Sublethal AgNPs resulted in increase of LC3II level and accumulation of autophagy related genes in HEK293T and A498 cells, which demonstrated AgNPs could activate autophagy at lower concentrations. Mechanistic investigation manifested that AMPK-mTOR signaling was enrolled in AgNPs-induced autophagy process rather than PI3K/AKT/mTOR signaling. In addition, P62 was elevated in AgNPs-treated cells in an mTOR-independent manner. We further uncovered that sublethal AgNPs exposure impaired the integrity and protease activities of lysosome. Together, our results revealed the mechanism by which AgNPs induced autophagy in renal cells under sublethal concentration.