The Role Of PGAM5/Drp1 In Mitochondrial Damage And Apoptosis In HT-22 Cells Upon Arsenite Exposure

Objective: Arsenic is a metalloid with cytotoxicity and is widely distributed in the natural environment.Long-term arsenic exposure can cause damage to multiple tissues and organs such as the nervous system,respiratory system,and cardiovascular system.Animal experiments and epidemiological investigations indicate damage to the nervous system caused by arsenic exposure.In this study,HT-22 cells were infected with sodium arsenite to investigate the mitochondrial damage and apoptosis of HT-22 cells induced by sodium arsenite via the PGAM5 / Drp1 signaling pathway.Provide corresponding experimental reference data.Methods:HT-22 cells were infected with different concentrations of sodium arsenite(0,4,6,8,10 μmol / L)for 24 hours.Western blot was used to measure PGAM5 /Drp1 protein expression level,ATP kit was used to measure cell ATP content,rhodamine 123 staining was used to detect mitochondrial membrane potential,and Annexin V-FITC/PI staining was used to detect cell apoptosis.Results:1.Sodium arsenite exposure can increase the expression level of the phosphoglycerate mutant PGAM5 protein in HT-22 cells,and the downstream protein Drp1 at the ser616 site significantly increases the phosphorylation level.At the same time,the ATP content in HT-22 cells decreased significantly;the mitochondrial membrane potential of the cells decreased significantly;the apoptosis level of HT-22 cells increased significantly,especially at a concentration of 10 μmol / L;2.After si RNA interfered with PGAM5,its downstream protein Drp1 was at ser616 The level of phosphorylation at the site decreased significantly;at the same time,the ATP content in HT-22 cells increased significantly;the mitochondrial membrane potential of the cells increased;and the level of apoptosis decreased significantly.Conclusions:1.Sodium arsenite induces increased expression of mitochondrial phosphoglycerate mutant PGAM5 and its downstream p-Drp1(Ser616)protein.2.PGAM5 / Drp1 signaling pathway mediates sodium arsenite-induced decrease in ATP levels,mitochondrial membrane potential and apoptosis in HT-22 cells.