已发表论文

纳米金颗粒的过胞吞作用增加缺氧人类肾小管细胞的自噬和凋亡

 

Authors Ding F, Li Y, Liu J, Liu L, Yu W, Wang Z, Ni H, Liu B, Chen P

Published Date September 2014 Volume 2014:9(1) Pages 4317—4330

DOI http://dx.doi.org/10.2147/IJN.S68685

Received 31 May 2014, Accepted 19 July 2014, Published 12 September 2014

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.
Keywords: gold nanoparticles (GNPs), toxicity, autophagy, apoptosis