Propofol may protect PC12 cells from β-amyloid₂₅₋₃₅ induced apoptosis through the GSK-3β signaling pathway / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 1884-1889, 2013.
Article
em En
| WPRIM
| ID: wpr-273077
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
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Índice:
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Assunto principal:
Fragmentos de Peptídeos
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Farmacologia
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Fosforilação
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Transdução de Sinais
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Propofol
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Sobrevivência Celular
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Peptídeos beta-Amiloides
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Células PC12
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Apoptose
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Quinase 3 da Glicogênio Sintase
Limite:
Animals
Idioma:
En
Revista:
Chinese Medical Journal
Ano de publicação:
2013
Tipo de documento:
Article