Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles

Sahu, Saura C.; Zheng, Jiwen; Yourick, Jeffrey J.; Sprando, Robert L.; Gao, Xiugong

doi:10.1002/jat.3170

Cited by 40 publications

(68 citation statements)

References 51 publications

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“…This agrees with a previous study of our group in which 4 h treatment of Caco-2 cells with similar sized and dosed AgNPs and AgNO 3 also induced more upthan downloaded genes, although this difference was not statistically significant (Bouwmeester et al, 2011). More up-than downregulation has also been reported for HepG2 cells treated with AgNPs (20 nm, 50 nm; 2.5 mg/ml; 4 and 24 h; Sahu et al, 2015) and A549 cells treated with AgNPs (16 nm; 12 mg/ml; 24 h) or Ag + (1.3 mg/ml; 24 h; Foldbjerg et al, 2012). In contrast, more down-than upregulated genes have been reported after exposure of 0.5 mg/ml AgNO 3 and 25 mg/ml 15 nm AgNPs to differentiated Caco-2 cells for 24 h (Bohmert et al, 2015).…”

Section: Transcriptomic Analysissupporting

confidence: 92%

“…MT1 and MT2 are isoforms found in all types of tissues, which were upregulated between 25 and 80FC, and 10 and 40FC on average in Caco-2 and MCF-7 cells, respectively. Previous studies exposing various cell types to metallic NPs also showed a high upregulation of MTs (Bajak et al, 2015;Bohmert et al, 2015;Bouwmeester et al, 2011;Foldbjerg et al, 2012;Moos et al, 2011;Sahu et al, 2015;Tuomela et al, 2013). Other highly upregulated genes connected to (oxidative) stress responses included heat shock proteins (HSPs), heme oxygenase 1 (HMOX1), Sulfiredoxin 1 (SRXN1) and Oxidative Stress Induced Growth Inhibitor 1 (OKL38).…”

Section: Mechanistic Responses In Caco-2 and Mcf-7 Cellsmentioning

confidence: 90%

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Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

et al. 2016

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The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag + and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO 3 were exposed for 6 h and 24 h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.

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Section: Transcriptomic Analysissupporting

confidence: 92%

Section: Mechanistic Responses In Caco-2 and Mcf-7 Cellsmentioning

confidence: 90%

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

et al. 2016

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“…The cysteines of MTs have been shown to bind oxidant radicals like superoxide and hydroxyl radicals [51], and MT expression has been implicated as a transient response to many forms of stress or injury [50]. Several previous studies [23, 24, 37, 52, 53] reported upregulation of HSPs and MTs in somatic cells following exposure to AgNPs. The upregulation of these proteins found in the current study suggests that AgNP exposure also induced cellular stresses and elicited cellular protective responses in ESCs.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of nano- and ionic silver to embryonic stem cells: a comparative toxicogenomic study

Gao¹,

Topping²,

Keltner³

et al. 2017

J Nanobiotechnol

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BackgroundThe widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag+) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs).ResultsThe present study characterized transcriptomic changes induced by 5.0 µg/ml AgNPs during spontaneous differentiation of mouse ESCs, and compared them to those induced by Ag+ under identical conditions. After 24 h exposure, 101 differentially expressed genes (DEGs) were identified in AgNP-treated cells, whereas 400 genes responded to Ag+. Despite the large differences in the numbers of DEGs, functional annotation and pathway analysis of the regulated genes revealed overall similarities between AgNPs and Ag+. In both cases, most of the functions and pathways impacted fell into two major categories, embryonic development and metabolism. Nevertheless, a number of canonical pathways related to cancer were found for Ag+ but not for AgNPs. Conversely, it was noted that several members of the heat shock protein and the metallothionein families were upregulated by AgNPs but not Ag+, suggesting specific oxidative stress effect of AgNPs in ESCs. The effects of AgNPs on oxidative stress and downstream apoptosis were subsequently confirmed by flow cytometry analysis.ConclusionsTaken together, the results presented in the current study demonstrate that both AgNPs and Ag+ caused transcriptomic changes that could potentially exert an adverse effect on development. Although transcriptomic responses to AgNPs and Ag+ were substantially similar, AgNPs exerted specific effects on ESCs due to their nanosized particulate form.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0265-6) contains supplementary material, which is available to authorized users.

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“…Based on these results, the authors conclude that silver nanoparticles have no specific impact on the gene expression of Caco‐2 cell‐based co‐culture and exposure to silver ions released from NP led to an upregulation of genes related to oxidative stress (metallothioneins, FOSB, FOSL1 and JUNB). Nevertheless, in addition to other reports (Carlson et al ., ; Choi and Hu, ; Sahu et al ., ), a size‐dependent toxicity of the NP was observed by Bouwmeester et al . ().…”

Section: Introductionmentioning

confidence: 97%

Proteomic responses of human intestinal Caco‐2 cells exposed to silver nanoparticles and ionic silver

Oberemm

Hansen

Böhmert

et al. 2015

J of Applied Toxicology

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Even although quite a number of studies have been performed so far to demonstrate nanoparticle-specific effects of substances in living systems, clear evidence of these effects is still under debate. The present study was designed as a comparative proteomic analysis of human intestinal cells exposed to a commercial silver nanoparticle reference material and ions from AgNO 3 . A two-dimensional gel electrophoresis/MALDI mass spectrometry (MS)-based proteomic analysis was conducted after 24-h incubation of differentiated Caco-2 cells with non-cytotoxic and low cytotoxic silver concentrations (2.5 and 25 μg ml À1 nanosilver, 0.5 and 5 μg ml À1 AgNO 3 ). Out of an overall number of 316 protein spots differentially expressed at a fold change of ≥ 1.4 or ≤ À1.4 in all treatments, 169 proteins could be identified. In total, 231 spots were specifically deregulated in particle-treated groups compared with 41 spots, which were limited to AgNO 3 -treatments. Forty-four spots (14 %) were commonly deregulated by both types of treatment. A considerable fraction of the proteins differentially expressed after treatment with nanoparticles is related to protein folding, synthesis or modification of proteins as well as cellular assembly and organization. Overlays of networks obtained for particulate and ionic treatments showed matches, indicating common mechanisms of combined particle and ionic silver exposure and exclusive ionic silver treatment. However, proteomic responses of Caco-2 cells treated with higher concentrations of silver species also showed some differences, for example regarding proteins related to fatty acid and energy metabolism, suggesting an induction of also some different molecular mechanisms for particle exposure and ionic treatment.

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Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles

Cited by 40 publications

References 51 publications

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

Toxicity of nano- and ionic silver to embryonic stem cells: a comparative toxicogenomic study

Proteomic responses of human intestinal Caco‐2 cells exposed to silver nanoparticles and ionic silver

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