| ObjectiveBrain injury after ischemia and reperfusion(I/R)results from a complex pathological process that involves multiple molecular mechanisms.Ferroptosis has been identified as a novel form of programmed cell death in the past decade.More recent studies have shown that ferroptosis is implicated in many neurological diseases including neurodegenerative diseases,stroke,and cancer.Ferroptosis suppressor protein1(FSP1)plays a significant role in inhibiting ferroptosis.This study aims to investigate the relationship between ferroptosis and ischemia-reperfusion injury and the effects of FSP1 on ferroptosis in PC12 cells with oxygen-glucose deprivation/reoxygenation(OGD/R)treatment.MethodsThe PC12 cells were induced by nerve growth factor and used to establish in vitro models.The expression of FSP1 was regulated by lentivirus transfection technology.Western blot and immunofluorescence were used to measure protein levels related to ferroptosis and the PI3K/AKT/GSK3β signal pathway.Cell viability was detected by CCK-8 assay and Calcein-AM/ Propidium Iodide(PI)staining.Mitochondrial structural morphology was checked by transmission electron microscopy in PC12 cells.Reactive oxygen species(ROS)and Malondialdehyde(MDA)were quantified using the relevant kits.ResultsOGD/R induced ferroptosis in PC12 cells,however,FSP1 overexpression reverses ferroptosis and promotes cell viability,lowering ROS and MDA content.The expression of FSP1 decreased in OGD/R0 h and OGD/R6 h and rebounded in OGD/R24 h and OGD/R48 h.During the processes of OGD/R-induced ferroptosis,FSP1 overexpression significantly stimulated PI3K/AKT/GSK3β pathway,but LY294002 weakens the protective effect of FSP1 overexpression.ConclusionOur outcomes demonstrate that overexpression of FSP1 markedly enhances the ability to resist ferroptosis via the PI3K/AKT/GSK3β pathway.The above results may provide a new preliminary lead for the treatment of the cerebral ischemia-reperfusion injury. |
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