The Protective Effects Of Erythropoietin On Apoptosis Of PC12 Cells Induced By β-amyloid Peptide

ObjectiveAlzheimer disease is the most common neurodegenerative disease.The causes and mechanisms of AD are very complicated.At present,Aβcan lead to AD through neurotoxicity and cell apoptosis which plays an important role in the pathogenesis of AD. Erythropoietin(EPO) plays a central role in erythropoiesis but also has neuroprotective properties.The recent discovery of a specific EPO receptor(EPOR) in the CNS has led to investigations in the neurotrophic and neuroprotective effects of EPO on the developing brain.Therefore,we explore the effect of EPO on apoptosis of Cells PC-12 injury by Aβ_25-35.MethodsCultured Cells PC-12 were divided into 3 groups:normal group,model group,EPO group.PC-12 cells were treated with different concentrations of EPO.PC-12 cells were routinely cultivated and treated by Aβ_25-35(final concentration,10μmol/L) 8 hours after the addition of EPO.Forty-eight hours later,cells were examined viability and apoptosis by MTT method and PI method,respectively.The ultrastructural changes of neuronal mitochondria were viewed under transmission electron microscope.The expression of Bcl-2 and cytochrome C(Cyt-C) were detected by western blot and immunohistochemistry.ResultsIt was revealed by MTT assay that various concentration of EPO could significantly prevent the cell viability induced by Aβ_25-35(P＜0.05).Pretreatment with 25U/ml EPO could significantly inhibit the viability decreasing induced by Aβ_25-35(P＜0.05).The number and morphology of neuronal mitochondria had distinct changes when compared with that of the model and EPO group.The expression rate of Bcl-2 protein in the EPO treated group was obviously higher than that in the model group.Cyt-C was weakly expressed in nerve cells of the Normal and the EPO group,but was strongly expressed in the model groupConclusionsDifferent doses of EPO administration can produce different effects.EPO at a dose of 25U/ml may be the optimal dose.EPO treatment can induce the expression of Bcl-2 protein and decrease the release of Cyt-C from mitochondria,thereby EPO can attenuate cell death and protect cell.Our conclusion would open a new window for the clinical treatment of Alzheimer disease.