摘要
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 Aβaccumulation 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.
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 Aβaccumulation 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.
基金
The present study was supported by the grants from the National Nature Science Foundation of China （No. 30872425） and Janssen Research Council China Foundation and Libang Anesthesiology R＆D Platform of Chinese Society of Anesthesiolgoy, Chinese Medical Association.
