Propofol may protect PC12 cells from induced apoptosis through the signaling pathway |
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Authors: | ZHANG Rui XU Jie LIU Yan-yong ZUO Ping-ping YANG Nan JI Chao WANG Yun WANG Hui WU An-shi and YUE Yun |
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Institution: | ZHANG Rui (Department of Anesthesiology, Weifang Medical University, Weifang,Shandong 261053, China);XU Jie (Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China);LIU Yan-yong (Department of Pharmacology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China);ZUO Ping-ping (Department of Pharmacology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China);YANG Nan (Department of Pharmacology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China);JI Chao (Department of Pharmacology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China);WANG Yun (Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China); |
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Abstract: | 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. |
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Keywords: | Propofol Alzheimer's disease Bcl-2/Bax Tau protein fl-amyloid GSK-3β |
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