University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
Toxicol Appl Pharmacol. 2013 Oct 15;272(2):519-28. doi: 10.1016/j.taap.2013.06.011. Epub 2013 Jun 22.
Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6h and 24h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24h at 0.1 and 5mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways.
银纳米粒子（AgNPs）的应用越来越广泛，因此人类和环境越来越多地接触到它们。然而，其潜在的毒理学影响还不完全清楚。在这里，我们研究了 AgNPs（平均粒径为 120nm）对体外和体内斑马鱼的影响，并将其与人肝癌细胞（Huh7）进行了比较。AgNPs 被整合到斑马鱼肝细胞（ZFL）和 Huh7 细胞以及斑马鱼胚胎中。在 ZFL 细胞中，AgNPs 导致活性氧（ROS）、内质网（ER）应激反应和 TNF-α的诱导。凋亡相关基因 p53 和 Bax 的转录也发生了改变。在 ZFL 和 Huh7 细胞中，转录谱不同。在 ZFL 细胞中，内质网应激标志物 BiP 在暴露于 0.5g/L 和 0.05g/L AgNPs 6h 和 24h 后分别被诱导，同时 ER 应激标志物 ATF-6 和剪接 XBP-1 也被诱导。这表明诱导了不同的内质网应激反应途径。此外，AgNPs 诱导 TNF-α。在暴露于 0.01、0.1、1 和 5mg/L AgNPs 的斑马鱼胚胎中，孵化受到影响，高浓度时出现形态缺陷。在 0.1 和 5mg/L AgNPs 暴露 24h 后，内质网应激相关基因转录物 BiP 和 Synv 显著上调。此外，凋亡相关基因 Noxa 和 p21 的转录也发生了改变。内质网应激反应在 ZFL 细胞中很强，在斑马鱼胚胎中也发生了。我们的数据首次证明 AgNPs 导致斑马鱼内质网应激的诱导。内质网应激的诱导可能会导致包括激活凋亡和炎症途径在内的几种后果。
