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Inhibitory effects of curcumin on H2O2-induced cell damage and APP expression and processing in SH-SY5Y cells transfected with APP gene with Swedish mutation

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, and the pathological mechanism of the disease is still far to understand. According to the amyloid cascade hypothesis in AD, Amyloid-β (Aβ) is considered as a key substance that contributes AD development. Aβ is a β-cleaving product from Amyloid-β protein precursor (APP). Mutations of APP including APPKM670/671670NL (Swedish mutation) result in Aβ overproduction and the development of early-onset familial AD. Increase of oxidative stress and damage also occurs in early stage of AD. In this study, we used a SH-SY5Y cell line that stably expresses APP gene with Swedish mutation (SH-SY5Y-APPswe), and the inhibitory effects of curcumin on H2O2-induced cell damage and APP processing were investigated. Cells were treated with curcumin (0 ~ 5 μM) for 4 h before hydrogen peroxide (H2O2). Cell growth was detected with CCK-8 assay, and cell damage was determined through the evaluation of release of lactate dehydrogenase (LDH) from the cytosol to the culture medium and the morphological change of nucleus. The ability of mitochondrial stress and the depolarization of mitochondrial membrane potential were assayed through the measuring the oxygen consumption rate (OCR) and the green/red fluorescence ratio of JC-1 dye respectively. The protein levels of APP, sAPPα, sAPPβ, and BACE1 were analyzed with Western blot assay. Aβ production was measured with enzyme-linked immunosorbent assay (ELISA). The results indicated that curcumin inhibits H2O2-induced decrease of cell growth and cell damage. Curcumin attenuates H2O2-induced damage on the ability to mitochondrial oxidative phosphorylation and membrane potential. Curcumin inhibits H2O2-induced increase of APP cleavage through β-cleavage pathway and of intracellular Aβ production. These results imply that curcumin can be used to treat AD through inhibiting oxidative damage-induced APP β-cleavage and intracellular Aβ generation.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (31471587), the Premium Funding Project for Academic Human Resources Development in Beijing Union University (BPHR2018CZ02), and Opening Project of Beijing Key Laboratory of Bioactive Substances and Functional Foods Beijing Key Laboratory (2019SPKF01).

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  1. Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, No. 197, Beitucheng West Road, Haidian District, Beijing, 100191, China

    Xi-Jun Song, He-Yan Zhou, Ya-Xuan Sun & Han-Chang Huang

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Song, XJ., Zhou, HY., Sun, YX. et al. Inhibitory effects of curcumin on H2O2-induced cell damage and APP expression and processing in SH-SY5Y cells transfected with APP gene with Swedish mutation. Mol Biol Rep 47, 2047–2059 (2020). https://doi.org/10.1007/s11033-020-05305-w

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