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Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles

Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiol...

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Published in:Toxicology and applied pharmacology 2016-05, Vol.299, p.8-23
Main Authors: Oh, Jung-Hwa, Son, Mi-Young, Choi, Mi-Sun, Kim, Soojin, Choi, A-young, Lee, Hyang-Ae, Kim, Ki-Suk, Kim, Janghwan, Song, Chang Woo, Yoon, Seokjoo
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Language:English
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Summary:Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10–200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. •This system served as a suitable model for developmental neurotoxicity testing.•Ag NPs induce the apoptosis in human neural cells by ROS generation.•Genes for development of neurons were dysregulated in response to Ag NPs.•Molecular events during early developmental neurotoxicity were proposed.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2015.11.004