Propofol may protect PC12 cells from β-amyloid₂₅₋₃₅ induced apoptosis through the GSK-3β signaling pathway.
- Author:
Rui ZHANG
1
;
Jie XU
;
Yan-Yong LIU
;
Ping-Ping ZUO
;
Nan YANG
;
Chao JI
;
Yun WANG
;
Hui WANG
;
An-Shi WU
;
Yun YUE
Author Information
- Publication Type:Journal Article
- MeSH: Amyloid beta-Peptides; pharmacology; Animals; Apoptosis; drug effects; Cell Survival; drug effects; Glycogen Synthase Kinase 3; metabolism; Glycogen Synthase Kinase 3 beta; PC12 Cells; Peptide Fragments; pharmacology; Phosphorylation; drug effects; Propofol; pharmacology; Rats; Signal Transduction; drug effects
- From: Chinese Medical Journal 2013;126(10):1884-1889
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDThere 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.
METHODSPC12 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.
RESULTSAβ25-35 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.
CONCLUSIONSThese 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.