Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation

Abstract

Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, due to their antibacterial properties. AgNPs are also being explored for the treatment of cancer in particular in combination with ionizing radiation. In this work, we studied the effects of AgNPs and ionizing radiation on mitochondrial redox state and function in a panel of lung cell lines (A549, BEAS-2B, Calu-1 and NCI-H358). The exposure to AgNPs caused cell cycle arrest and decreased cell proliferation in A549, BEAS-2B and Calu-1, but not in NCI-H358. The mitochondrial reactive oxygen species (ROS) and protein oxidation increased in a time- and dose-dependent manner in the more sensitive cell lines with the AgNP exposure, but not in NCI-H358. While ionizing radiation also induced changes in the mitochondrial redox profiles, in general, these were not synergistic with the effects of AgNPs with the exception of NCI-H358 and only at a higher dose of radiation.

<p>Silver Nanoparticle-Induced Apoptosis in ARPE-19 Cells Is Inhibited by <em>Toxoplasma gondii</em> Pre-Infection Through Suppression of NOX4-Dependent ROS Generation</p>

“…These results indicated that AgNP-treated ARPE-19 cells prominently induced mitochondrial apoptosis in a concentration-dependent manner, which agrees with several different reports of cellular toxicity after AgNP exposure. [7][8][9]29 Polydopaminecoated branched Au-Ag NPs induce an increase in BAX and decrease in Bcl-2 levels, and further provoke depolarization of the MMP and caspase-8 and caspase-3 activation, ultimately causing apoptosis in T24 human bladder cancer cells. 29 Regarding the mechanism of AgNP-induced toxicity, De Matteis et al 6 described that endocytosed AgNPs are degraded in the lysosomes and the release of Ag + ions in the cytosol induces cell damages, while ions released in the cell culture medium have a negligible effect.…”

“…According to previous studies, mitochondrial ROS may be involved in the activation of caspases and MAPKs 18,22,23 and is responsible for the apoptosis-inducing effects of AgNPs. [3][4][5][6][7] We evaluated whether T. gondii pretreatment suppressed AgNPtriggered intracellular ROS production in ARPE-19 cells. The cells were pre-infected with T. gondii at MOI 5 for 2 h and treated with or without 5 μg/mL AgNPs for 24 h. We then evaluated ROS production using MitoSOX red mitochondrial superoxide indicator that specifically detects ROS produced within mitochondria.…”

“…4,5 And the strong oxidative activity of AgNPs releases silver ions, which have several negative effects on biological systems by inducing cytotoxicity, genotoxicity, immunological responses, and even cell death. [4][5][6] The cytotoxicity of AgNPs has been examined in several in vitro studies using human lung cell lines, 7 human liver cell lines, 8 and others. In animal eye tissues, AgNPs suppress the proliferation and migration of bovine retinal endothelial cells and exhibit an antiangiogenic potential, 9 as well as induce significant neurotoxic effects in in vitro-cultured mouse retinal tissues.…”

Dual-Reactivity trans-Cyclooctenol Probes for Sulfenylation in Live Cells Enable Temporal Control via Bioorthogonal Quenching

“…19,20 Dimedone and BCN derivatives have both been used to covalently modify sulfenic acids in living cells. 17,[21][22][23][24][25][26] However, these reagents remain active at the point of cell lysis, relying on additives to quench sulfenic acids during work up. Ideally, sulfenic acid probes could instead be fully quenched in live cells, as cell lysis may promote subsequent unwanted redox transformations.…”

Roles of ROS&nbsp;and Cell Cycle Arrest in the Genotoxicity Induced by Gold Nanorod Core/silver Shell Nanostructure&nbsp;

“…The major mechanisms for AgNP-induced genetic injuries are considered to be the overproduction of reactive oxidative species, in ammation, and cell cycle disturbance [9,10]. As suggested in previous studies, AgNPs could either directly interact with DNA via oxidative damage [11] and interfere in the interphase at the DNA level and mitosis at the chromosomal level, or interact with the nucleoprotein and mitotic spindle apparatus to disturb cell cycle checkpoints [12]. However, whether the genotoxicity induced by AgNPs is partially attributable to the nanoparticles [13,14] or completely to the released Ag + ions is still unclear [15,16].…”