Propofol may protect PC12 cells from β-amyloid25-35 induced apoptosis through the GSK-3β signaling pathway

Background There are two major pathological hallmarks of Alzheimer'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 Aβ 25-35 were added to determine a proper concentration for further study. After exposure to 10 μmol/L Aβ 25-35 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 Aβ 25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 μmol/L Aβ 25-35 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 Aβ 25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ 25-35 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 Aβ 25-35 . Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation. Conclusions These data indicate that propofol may protect PC12 cells from Aβ 25-35 -induced apoptosis and tau hyperphosphorylation through the GSK-3β pathway, therefore it may be a safer anesthesia for AD and elderly patients.