Small Molecule Compounds Alleviate Anisomycin-induced Oxidative Stress Injury in SH-SY5Y Cells Via Downregulation of P66shc and Aβ1-42 Expression
Overview
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Oxidative stress and ageing are important factors contributing to the pathogenesis of Alzheimer's disease (AD), which is associated with neuronal damage and β-amyloid (Aβ) deposition. The p66shc adaptor protein is important for the regulation of oxidative stress and ageing. In the present study, SH-SY5Y human neuroblastoma cells were treated with anisomycin in order to establish a cell model of oxidative stress-induced neuronal damage. The results from quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting demonstrated that anisomycin was able to stimulate the secretion of Aβ1-42 from SH-SY5Y cells and upregulate the expression levels of p66shc, which was associated with concomitant damage to SH-SY5Y cells. In addition, the protective effects of various small molecule compounds with antioxidant properties against neuronal damage were evaluated. Notably, treatment of SH-SY5Y cells with gallic acid was associated with significant downregulation of p66shc protein expression levels, reduced anisomycin-induced secretion of Aβ1-42, and increased superoxide dismutase activity and acetylcholine secretion levels. The results of the present study suggested that anisomycin is able to promote oxidative neuronal damage by inducing the secretion of Aβ1-42 from neurons and increasing the neuronal expression of p66shc, and this damage may be attenuated by treatment with gallic acid. Therefore, gallic acid and similar small molecule compounds may be considered for the alleviation of neuronal oxidative stress injury in patients with AD.
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