Penehyclidine Hydrochloride Inhibits Ferrous Myoglobin Induced Ferroptosis of Human Renal Cortex Proximal Tubule Epithelial Cells
Objective To explore the role and mechanism of penehyclidine hydrochloride(PHC)on ferroptosis induced by ferrous myoglobin in human renal cortex proximal tubule epithelial(HK2)cells.Methods HK2 cells were treated with 6mg/ml ferrous myoglo-bin to establish rhabdomyolysis(RM)induced acute kidney injury(AKI)cell models.PHC and ferrous myoglobin were added to incu-bate the cells.The ferrostatin-1(Fer-1,ferroptosis inhibitor)and Erastin(ferroptosis inducer)were then employed as experimental interventions.The cell activity was determined by CCK-8method,and the level of Fe2+ and MDA were detected by assay kits,the level of lipid reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected by flow cytometry.The protein and mRNA expression levels of GPX4 were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and Western bolt(WB).Results PHC treatment significantly increased the cell activity,decreased the levels of Fe2+,ROS,MDA.and increased the level of MMP.Compared with PHC alone treatment,the addition of Fer-1 increased cell activity further,down-regulated the level of Fe2+,decreased the levels of ROS and MDA,and increased the level of MMP.After adding Erastin,the results were be opposited.In addition,PHC treatment mechanistically up-regulated the levels of SLC7A11 and GPX4.Conclusion PHC can protect HK2 cells from ferromyoglobin damage by inhibiting ferroptosis,which may be related to the SLC7A11/GPX4 pathway.
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