Aggravation Effect of Isoflurane on Aβ25–35-Induced Apoptosis and Tau Hyperphosphorylation in PC12 Cells

Some anesthetics have been suggested to induce Alzheimer’s disease (AD) neuro-pathogenesis. Increasing evidence indicates that hyperphosphorylated tau plays a key role in the pathogenic events that occur in AD. Isoflurane has been shown to induce apoptosis, which leads to accumulation of amyloid-β (Aβ). We set out to investigate whether isoflurane can induce apoptosis by increasing hyperphosphorylated tau in Aβ25–35-induced cells and the underlying mechanism. Cultured rat pheochromocytoma cells (PC12) were exposed to 20 mM Aβ25–35 alone or with 2 % isoflurane for 6 h. The cell viability was determined by MTT assay, and the apoptosis rate was detected by flowcytometry. Western blotting and immunocytochemical staining were performed to observe the protein expression of Bcl-2 family, tau phosphorylation of different sites, tau protein kinases and phosphatases. Additionally, lithium chloride was administered to all above groups to investigate the changes of apoptosis rate and protein expression. The apoptosis rate was significantly increased in Aβ25–35 group compared with the others groups, which was accompanied by bcl-2 decline, and the phosphorylation of glycogen synthase kinase-3β(GSK-3β) and tau of two sites increased. LiCl attenuated the cellular apoptosis by inhibition the level of tau phosphorylation. Isoflurane upregulated the level of phosphorylated GSK-3β, which phosphorylate tau at different sites, and aggravated the apoptotic rate of the Aβ25–35-induced PC12 cells. It indicated that isoflurane-induced tau phosphorylation might play a role in the AD-like development.