Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation

Huo, Lingling; Chen, Rui; Zhao, Lin; Shi, Xiaofei; Bai, Ru; Long, Dongyang; Chen, Feng; Zhao, Ye; Chang, Yan; Chen, Chunying

doi:10.1016/j.biomaterials.2015.05.029

Cited by 132 publications

(100 citation statements)

References 35 publications

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“…In addition to the analyses of the induction of proinflammatory factors we also examined whether cell stress might occur in ECs after exposure to nanoparticles. Several studies have previously shown induced endoplasmic reticulum (ER) stress in different cell types after treatment with silverdoped silica NPs, 40 silver NPs 41,42 or polystyrene nanospheres. 43 Chen et al showed that zinc oxide NPs triggered ER stress in HUVEC 44 and gold NPs were shown to induce stress signaling in K562 cells.…”

Section: Resultsmentioning

confidence: 99%

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

et al. 2017

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a PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood-brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood-brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream.

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Section: Resultsmentioning

confidence: 99%

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

et al. 2017

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“…In order to protect the cells against nanoparticle-mediated toxicity, the ER rapidly responds with the unfolded protein response (UPR), an important cellular self-protection mechanism [134]. The ER stress system contains three dominant stress sensors, IRE1, PERK, and ATF-6 [135]. For instance, the activation of the ER stress signaling pathway was observed by upregulated expression of xbp-1s, chop/DDIT3, TRIB3, ADM2, BIP, Caspase-12, ASNS, and HERP at either the mRNA and/or protein levels in 16HBE cells.…”

Section: Activation Of Signaling Molecules In Response To Agnps Inmentioning

confidence: 99%

“…For instance, the activation of the ER stress signaling pathway was observed by upregulated expression of xbp-1s, chop/DDIT3, TRIB3, ADM2, BIP, Caspase-12, ASNS, and HERP at either the mRNA and/or protein levels in 16HBE cells. Conversely, there was no significant upregulation in HUVECs or HepG2 cells [135]. Simard et al [136] attributed ER stress-mediated apoptosis to low and high concentrations of 15 nm AgNPs.…”

Section: Activation Of Signaling Molecules In Response To Agnps Inmentioning

confidence: 99%

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Zhang

Shen

Gurunathan

2016

IJMS

241

137

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Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives on research into AgNPs.

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“…In recent decades, increasing numbers of studies have provided evidence for the toxicity of AgNPs in various cells and organisms, and the mechanisms for these effects have also been investigated (Huo et al, ; Johnston et al, ; Shi, Sun, Zou, & Zhang, ; Wang, Xia, & Liu, ). At the cellular level, AgNPs can induce abnormal cellular morphologies, suppress cell growth and disturb the normal functions, as well as damage the genetic integrity, which causes cell cycle arrest in the G 2 /M phase, possibly due to the repair of damaged DNA (AshaRani, Low Kah Mun, Hande, & Valiyaveettil, ).…”

Section: Introductionmentioning

confidence: 99%

NOX4‐ and Nrf2‐mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells

Sun

Yang

Shi

et al. 2017

J of Applied Toxicology

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It has been widely reported that silver nanoparticles (AgNPs) induce oxidative stress in various cell lines. However, the mechanism for this effect and its consequences for cellular signaling are poorly understood. In this study, human umbilical vein endothelial cells (HUVECs) were used to assess the toxicity and investigate the associated molecular mechanisms caused by exposure to AgNPs. We demonstrated that AgNP exposure significantly and dose-dependently decreased the cell viability, induced reactive oxygen species (ROS) generation and led to early apoptosis in HUVECs. Our findings showed that AgNPs induced excess ROS production that affected the signaling pathways by a mechanism that depended on activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity through upregulation of NADPH oxidase 4 (NOX4) protein expressions. Moreover, AgNPs could disrupt the inactivation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response, which is considered another important element for oxidative stress caused by AgNPs in HUVECs. The redox imbalance between NOX4 and Nrf2 was an important cause for the ROS overproduction that led to cell injury in HUVECs. The results provided insight into the mechanisms of oxidative stress induced by AgNPs in vascular endothelial cells.

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Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation

Cited by 132 publications

References 35 publications

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

NOX4‐ and Nrf2‐mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells

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