The role of deferoxamine in methylmercury-induced ferroptosis and its mechanism#br#
LIU Ting-ting 1,2, DONG Li-hua 1, ZHANG Yu 1, XU Wei 1, ZHU Hai-tao3,#br#
LI Fang 1, WANG Su-hua 1, XING Guang-wei 1, LU Rong-zhu 1#br#
(1. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013; 2. Department of Laboratory, Changzhou First People′s Hospital, Changzhou Jiangsu 213000; 3. Department of Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China)
Objective: To investigate the role of deferoxamine pretreatment on the toxicity of methylmercury and its potential mechanism. Methods: PC12 and BRL cells were selected and divided into groups: control group, cells were cultured with high sugar medium containing with 10% fetal bovine serum for 0.5 h; methylmercury group, cells were treated with different concentrations (1.0, 2.5, 5.0, 10.0 μmol/L) of methylmercury for 0.5 h, MTT assay was used to detect cell viability, Western blotting was used to detect the expression of glutathione peroxidase 4 (GPx4). The above two results were used to screen the optimal concentration of methylmercury. In addition, PC12 cells and BRL cells were divided into control group which cells were cultured with high sugar medium containing with 10% fetal bovine serum for 6.5 h, and different concentrations of deferoxamine + methylmercury groups which cells were pretreated with 0, 50, 100, 200 and 400 μmol/L deferoxamine for 6 h, then treated with methylmercury (10.0 μmol/L) for 0.5 h, Western blotting assay was used to detect the expression of GPx4 and hypoxia inducible factor-1α(HIF-1α), MTT assay was used to detect cell viability. Results: Compared with the control group, 10.0 μmol/L methylmercury group was shown with significantly decreased cell viability in both cell lines, therefore, 10.0 μmol/L methylmercury was used for subsequent experiments. Compared with 0 μmol/L deferamine+ methylmercury group, the expression of GPx4 and HIF-1α enhanced with the increase of deferamine concentration in both cell lines; cell viability was enhanced when deferoxamine concentration reached to 400 μmol/L in PC12 cells and 200 μmol/L in BRL cells. Conclusion: Deferoxamine may antagonize methylmercury-induced ferroptosis through upregulating the expression of HIF-1α and GPx4.