Dexmedetomidine inhibits ferroptosis of human renal tubular epithelial cells by activating the Nrf2/HO-1/GPX4 pathway
Objective To investigate the protective effect of dexmedetomidine(DEX)against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells)and explore the underlying mechanism.Methods HK-2 cells were treated with erastin alone or in combination with different concentrations(2.5,5.0 and 10 μmol/L)of DEX,and the changes in cell viability were observed using CCK-8 assay.To explore the mechanism by which DEX inhibits erastin-induced ferroptosis,HK-2 cells were treated with erastin,erastin+10 μmol/L DEX,or erastin+10 μmol/L DEX+ML385(a Nrf2 inhibitor),after which the cell viability was assessed.The level of intracellular Fe2+was detected by cell ferrous iron colorimetric assay kit,and flow cytometry was performed to detect reactive oxygen species(ROS);MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells;The expressions of Nrf2,HO-1 and GPX4 proteins were detected by Western blotting.Results Erastin treatment significantly inhibited the viability of the cells,decreased GSH content,and increased intracellular levels of Fe2+,ROS and MDA.The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells,increased GSH content,reduced the levels of Fe2+,ROS and MDA,and upregulated the protein expressions of Nrf2,HO-1 and GPX4 in the cells.The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway,decreased the cell viability and GSH content,and increased the levels of Fe2+,ROS and MDA in HK-2 cells.Conclusion The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.
万方数据
维普
