Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China; Department of Gynecology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Ecotoxicol Environ Saf. 2018 Dec 30;166:71-77. doi: 10.1016/j.ecoenv.2018.09.070. Epub 2018 Sep 21.
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.
随着纳米技术的发展和独特性质的出现，银纳米粒子（AgNPs）已经广泛应用于我们的工作和生活中。然而，纳米安全性问题仍未得到充分理解。尽管越来越多的研究记录了在有毒剂量下 AgNPs 介导的自噬作用，但很少有研究揭示在非毒性浓度下 AgNPs 诱导自噬的机制。在这里，我们研究了亚致死浓度下 AgNPs 对肾细胞自噬的生物学效应。亚致死浓度的 AgNPs 导致 HEK293T 和 A498 细胞中 LC3II 水平升高和自噬相关基因的积累，表明 AgNPs 在较低浓度下可以激活自噬。机制研究表明，AMPK-mTOR 信号通路参与了 AgNPs 诱导的自噬过程，而不是 PI3K/AKT/mTOR 信号通路。此外，AgNPs 处理的细胞中 P62 的水平以 mTOR 非依赖性方式升高。我们进一步发现，亚致死浓度的 AgNPs 暴露会损害溶酶体的完整性和蛋白酶活性。综上所述，我们的研究结果揭示了亚致死浓度下 AgNPs 诱导肾细胞自噬的机制。
