中华医学杂志：英文版, 2013 (10), p.1884-1889
2013
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- Titel
- Propofol may protect PC12 cells from p-amyloid25-35 induced apoptosis through the GSK-3β signaling pathway
- Ist Teil von
- 中华医学杂志：英文版, 2013 (10), p.1884-1889
- Erscheinungsjahr
- 2013
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- EZB Free E-Journals
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- 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 desfiurane, 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 IJmol/L to 80 μmol/L of aggregated Aβ2s.ss were added to determine a proper concentration for further study. After exposure to 10μmol/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 pmol/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-313 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 IJmol/L β25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation. Conclusions These data indicate that propofol may protect PC12 cells fromβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-313 pathway, therefore it may be a safer anesthesia for AD and elderly patients.