Propofol may protect PC12 cells from induced apoptosis through the signaling pathway

Background There are two major pathological hallmarks of AIzheimer's disease.One is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques； the other is hyperphosphorylated tau,causing neuronal apoptosis.Some inhalation anesthetics,such as isoflurane and desflurane,have been suggested to induce Aβ accumulation and cause AD-like neuropathogenesis.Whether intravenous anesthetics have similar effects is still unclear.We therefore set out to determine the relationship between propofol and AD-like pathogenesis.Methods PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment.Various concentrations from 5 μmol/L to 80 μmol/L of aggregated Aβ25-35 were added to determine a proper concentration for further study.After exposure to 10 μmol/L Aβ25-35 alone or with 20 μmol/L propofol for 6 hours,PC12 cell viability was determined by MTT assay.Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family,tau phosphorylation at different sites,and tau protein kinases and phosphatases.Results Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner.Exposure to 10 μmol/L Aβ25-35 for 6 hours resulted in the mild cell survival,accompanied by a decline in Bcl-2,and an increase in phosphorylation of GSK-3β and tau at different sites.Compared with the Aβ25-35 group,cells treated with propofol alone showed no significant difference,while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate (P ＜0.01 or P ＜0.05).Tau phosphorylation at Ser396,Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 μmol/L Aβ25-35.Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation.Conclusions These data indicate that propofol may protect PC12 cells from Aβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-3β pathway,therefore it may be a safer anesthesia for AD and elderly patients.