Salidroside regulates neuronal ferroptosis induced by oxygen glucose deprivation/reperfusion by regulating the Nrf2/ARE signaling pathway
Objective To investigate the regulatory effects of salidroside on neuronal iron death induced by oxygen glucose deprivation/reperfusion(OGD/R)by regulating the nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods Mouse neuronal cells HT22 were treated with blank control,induced with OGD/R,OGD/R+low-dose salidroside(20μmol/L),OGD/R+high-dose salidroside(40μmol/L),OGD/R+ high-dose salidroside(40μmol/L)+ ML385(Nrf2 inhibitor,1μmol/L).Cell viability and proliferation were detected by MTT assay and CCK-8 assay,respectively.Intracellular iron concentration was measured using an iron assay kit.Activities of glutathione peroxidase 4(GPX4),superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)were measured using commercial kits.Changes in the ultrastructure of mouse neurons were observed by transmission electron microscopy.Western Blot was applied to detect the expressions of GPX4,COX2,ACSL4,and associated proteins in the Nrf2/ARE signaling pathway.Results Compared with those treated with blank control,mouse neurons induced with OGD/R presented damaged ultrastructure of neuronal cells,mitochondrial shrinkage,disappearance of the mitochondrial cristae,ruptured outer membrane,significantly lower cell viability,proliferation rate,activities of GPX4 and SOD,and protein expressions of Nrf2,HO-1,and GPX4,but significantly higher Fe2+ concentration,activities of MDA and ROS,and protein expressions of COX2 and ACSL4(P<0.05).Compared with those induced with OGD/R,cells induced with OGD/R+low-dose salidroside(20μmol/L)and OGD/R+high-dose salidroside(40μmol/L)presented significantly improved ultrastructure,significantly increased cell viability,proliferation rate,activities of GPX4 and SOD,and protein expressions of Nrf2,HO-1,and GPX4,and significantly reduced Fe2+ concentration,activities of MDA and ROS,and protein expressions of COX2 and ACSL4(P<0.05).Compared with those induced with OGD/R + high-dose salidroside(40μmol/L),the above indexes were significantly reversed in cells induced with OGD/R+ high-dose salidroside(40μmol/L)+ML385(Nrf2 inhibitor,1μmol/L).Conclusion Salidroside can inhibit OGD/R-induced neuronal ferroptosis by activating the Nrf2/ARE signaling pathway.
salidrosidenuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)oxygen glucose deprivation/reperfusionneuronferroptosis
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