The toxic effect of lithium ion on neurons (PC12 cells) and Aβ42 molecules
Wang Yang1, Zhang Yan, Zhang Hongjing
1Department of Psychiatry, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Abstract:
In this study, the neurotoxicity of Li ion and its effect on the morphologies of Aβ42 molecules were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fluorescence (FL), atomic force microscopy (AFM), and circular dichroism (CD) spectroscopy. MTT assays show that Li ion with a dosage level lower than 50 mg/l did not show detectable cytotoxicity on pheochromocytoma (PC12) cells whereas a dosage level higher than 100 mg/l resulted in significant cytotoxicity. The interaction between Aβ42 and Li ion occurs, and the quenching effect of Li ion on the fluorescence emission of AΒ42 is found to be concentration dependent, suggesting that Li ion can bind to the Aβ42 molecules. CD results suggest that a more incompact conformation state will be adopted upon the interaction between Aβ42 and Li ion. According to AFM images, Li ion could induce the formation of the fibrils after incubation for 3 or 5 days. The formation of the oligomer and fibrils originates from the strong interactions between Aβ42 and Li ion. Li ion could accelerate the random coil Aβ42 monomers aggregating into the β-sheet fibrils, which would induce the neurotoxic effect.
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