Selenium and Zinc against Aβ25–35-Induced Cytotoxicity and Tau Phosphorylation in PC12 Cells and Inhibits γ-cleavage of APP
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Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aβ25–35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 μmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aβ25–35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aβ25–35,10 mmol/L Aβ25–35 + 0.1 μmol/L Se, 10 mmol/L Aβ25–35 + 0.1 μmol/L Zn, 10 mmol/LAβ25–35 + 0.1 μmol/L Se + 0.1 μmol/L Zn, or 0.1 μmol/L Se + 0.1 μmol/L Zn. The result showed that cell viability was decreased in MTT metabolic rate; LDH release and MDA, H2O2, and NO levels were increased and the GSK-3β and phosphorylated tau protein level were increased in Aβ25–35-treated group (P < 0.05 or P < 0.01), which whole changes were attenuated by Se and Zn and Se combined Zn. In order to evaluate whether the Se and Zn have an effect on processing pathway of amyloid precursor protein (APP), we examined the activity of γ-secretase in primary cultured cortical neuron cells. ELISA analysis showed that Se and Zn could inhibit the activity of γ-secretase. Then we also investigated the effect of Se and Zn on the Aβ1–40 concentration and APP-N-terminal fragment expression from APP695 stably transfected Chinese hamster ovary (CHO) cells. APP695 stably transfected CHO cells were treated with 0.1 μmol/L Se and Zn; cells were divided into control and four treated groups, which received either 0.5 M DAPT, 0.1 μmol/L Se, 0.1 μmol/L Zn, or 0.1 μmol/L Se + 0.1 μmol/L Zn. Se and Zn could decrease Aβ1–40 production and increase the APP-N-terminal fragment protein expression. These experiments indicate that Se and Zn have a protective effect on AD pathology that a possible mechanism is inhibiting the activity of γ-secretase to decreasing Aβ1–40 production further influencing the APP processing. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.
KeywordsSelenium Zinc Aβ25–35 Tau APP γ-secretase Alzheimer’s disease
This work was financially supported by the Research Fund of Jilin Provincial Education Department (2016-279) and the National Science Foundation of China (81160159) and China Scholarship Council (2016-3192).
- 8.Zheng R, Zhang ZH, Chen C, Chen Y, Jia SZ, Liu Q, Ni JZ, Song GL (2017) Selenomethionine promoted hippocampal neurogenesis via the PI3K-Akt-GSK3β-Wnt pathway in a mouse model of Alzheimer’s disease. Biochem Biophys Res Commun 17:30103–30101Google Scholar
- 12.Xu YJ (2011) Effect of selenium and zinc on deficit of learning and memory and the levels of MDA & NO in dementia mice model. J Nutr (China J) 33(2):118–120Google Scholar
- 14.Haass C, Selkoe D (1994) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell 7:1039–1042Google Scholar
- 29.Takashima A, Honda T, Yasutake K, Michel G, Murayama M, Murayama O, Ishiguro K, Yamaguchi H (1998) Activation of tau protein kinase I/glycogensynthase kinase-3beta by amyloid beta peptide (25–35) enhances phosphorylation of tau in hippocampal neurons. Neurosci Res 31:317–323CrossRefPubMedGoogle Scholar
- 33.Leschik J, Welzel A, Weissmann C, Eckert A, Brandt R (2007) Inverse and distinct modulation of tau-dependent neurodegeneration by presenilin 1 and amyloid-b in cultured cortical neurons: evidence that tau phosphorylation is the limiting factor in amyloid-b-induced cell death. J Neurochem 101:1303–1315CrossRefPubMedGoogle Scholar