Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium up -take in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high cor-relation coefficient (r =-0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

Automated summary

The objective of this study was to investigate the endocytosis mechanisms of uranium uptake in HK-2 cells and assess its toxic effects. Results showed that uranium exposure disrupted redox homeostasis, increased cell membrane permeability and mitochondrial membrane permeability, leading to apoptosis via cytochrome-c leakage. The alkaline phosphatase activity increased after uranium exposure, suggesting intracellular mineralisation of uranium and subsequent cell necrosis. Furthermore, clathrin-mediated endocytosis played a crucial role in uranium uptake in HK-2 cells, and there was a strong negative correlation (r = -0.853) between total uranium uptake and cell viability according to Pearson correlation analysis. In conclusion, uranium uptake in mammalian cells was mainly facilitated by clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, apoptosis, and necrosis.