Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells

Abstract

anomaterials are currently used in a wide range of products with more prospective applications; however, people raised concerns about their safety profiles. This is because nanomaterials have novel physicochemical properties that can interact with biological systems to generate toxicity. 1 To date, most studies have focused on cytotoxicity of nanomaterials at high concentrations that incur significant injuries to cells in vitro and in animals; however, the high dosage used is often not realistic and fails to consider the potentially detrimental effects on human health under chronic lowdose exposure settings, such as everyday and environmental exposure. 2 Thus, research is urgently needed to study the biological effects at sublethal or even nontoxic concentrations. Nanosilver (nAg), a material that is well-known for its antimicrobial properties, has been extensively used in a wide range of biomedical and consumer products. 3À6 Although many studies have been performed to investigate the cytotoxicity of nAg under different settings, 7À9 relatively little study has been conducted to understand the biological effects of nAg under nontoxic concentrations, which likely precede the toxicological processes or can be differentiated from cytotoxic effects but could perturb cellular homeostasis.Under normal conditions, cells maintain a balanced energy homeostasis through concertedly regulated signaling and metabolic pathways. Namely, there is a perfect equilibrium between anabolism and catabolism

Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

“…As shown in Fig. 2A, AgNPs did not significantly reduce the viability of MEL cells until the concentration reached 12 mg/mL, similar to our previous finding [26,41]. As a result, sublethal concentrations at 8 mg/mL and lower were chosen in the current study.…”

“…The zeta-potential analysis showed that AgNPs were negatively charged in culture medium over the time course (Fig. 1C), analogous to those used in our past studies [26,41]. We performed cytotoxicity screening in MEL cells treated with AgNPs at various concentrations.…”

“…We recently demonstrated that AgNPs could directly bind to RNA polymerase, leading to interruption of the transcription machinery and thus a drop of overall RNA synthesis in MEL cells at low concentrations without triggering detectable ROS [26]. Moreover, we demonstrated that AgNP treatment reprogrammed cellular energy homeostasis by switching from oxidative phosphorylation-based aerobic metabolism to anaerobic glycolysis in order to satisfy the basal energy demand for cell survival in both tumor cells and nontumor cells in response to sublethal AgNPs [41]. These findings highlight the potential toxicity of AgNPs to various cells at sublethal concentrations.…”

miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2

“…Western blotting analysis was performed, as described previously [40]. Antibodies (Abs) against ATF4, Nrf2, GAPDH and FLAG were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA).…”

“…Briefly, cells were cross-linked with 1 % formaldehyde at room temperature for 10 min, and were then washed with cold PBS. Fixed cells were re-suspended in lysis buffer with SDS, followed by sonication of chromatin into fragment sizes ranging from 200 to 1000 bp as previously described [40]. After sonication, the supernatant containing chromatin was diluted in ChIP dilution buffer, and was subjected to incubation with Abs against IgG, Nrf2 and H3K27me3.…”