Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Abstract

Background Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells. Results Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death. Conclusion/significance Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use–especially for the potential GNP-related therapies in chronic kidney disease patients.

Silver nanoparticles outperform gold nanoparticles in radiosensitizing U251 cells in vitro and in an intracranial mouse model of glioma

“…51 Contrary to the role of autophagy triggered by most nanomaterials, our recently reported studies have revealed that autophagy initiated by AgNPs or/and radiation mediates cytoprotective effect, which is believed to serve as a pro-survival process of cells facing AgNPs and their associated radiation. 49,52 Given that both AuNPs and AgNPs belong to the noble metal nanoparticles, and the roles of their enhanced autophagy are the same, 49,53 this could indicate that autophagy activated by AuNPs plus radiation may be similar in function to that by AgNPs plus radiation. Since protective autophagy antagonizes apoptotic cell death induced by cancer chemotherapy and radiation therapy, 54,55 pharmacological inhibition of this type of autophagy should enhance the anticancer activity of AuNPs alone, AgNPs alone, or their combination with radiation, in particular that of AgNPs-based treatment.…”

PM2.5 exposure induced renal injury via the activation of the autophagic pathway in the rat and HK-2 cell

“…The kidney is an organ with rich and diverse endothelial cells (Verma and Molitoris, 2015). Ding et al found that gold nanoparticles could induce autophagy of hypoxic human proximal tubule epithelial (HK-2) cells (Ding et al, 2014). The basal autophagy in the kidney is vital for the normal homeostasis of proximal tubules, but abnormal autophagy can impair renal function and increased p62 levels and oxidative stress (Kaushal and Shah, 2016;Lin et al, 2019).…”

Copper nanoclusters trigger muscle cell apoptosis and atrophy in vitro and in vivo

“…Our data demonstrated that treatment with CuNCs significantly decreased the mitochondrial membrane potential in C2C12 myoblasts. Similar results were obtained by Karlsson and coworkers, who suggested that exposure to CuO nanoparticles can cause mitochondrial depolarization (Ding et al ., ; Karlsson et al ., ).…”