title: Aggravation effect of isoflurane on Aβ(25-35)-induced apoptosis and tau hyperphosphorylation in PC12 cells.
abstract: 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.
authors: Department of Anesthesiology, Beijing Chao Yang Hospital, Capital Medical University, No.8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.
authors: Jie
authors: J
authors: Xu
authors: Rui
authors: R
authors: Zhang
authors: Pingping
authors: P
authors: Zuo
authors: Nan
authors: N
authors: Yang
authors: Chao
authors: C
authors: Ji
authors: Weiran
authors: W
authors: Liu
authors: Yun
authors: Y
authors: Wang
authors: Hui
authors: H
authors: Wang
authors: Anshi
authors: A
authors: Wu
authors: Yun
authors: Y
authors: Yue
authors: Yanyong
authors: Y
authors: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007530:Isoflurane / Q000633:toxicity*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D007530:Isoflurane