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Syringin Prevents Aβ25–35-Induced Neurotoxicity in SK-N-SH and SK-N-BE Cells by Modulating miR-124-3p/BID Pathway

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder disease, disturbing people’s normal life. Syringin was mentioned to antagonize Amyloid-β (Aβ)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aβ-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid β-protein fragment 25–35 (Aβ25–35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aβ25–35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aβ25–35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aβ25–35-induced injuries. Syringin protected against Aβ25–35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aβ25–35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD.

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Author notes

  1. Nan Zhang and Li Zhao have contributed equally to this paper.

Authors and Affiliations

  1. Department of Geriatrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Nan Zhang

  2. Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China

    Li Zhao

  3. Public Health Division, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Feilong Zhang

  4. Department of Neurosurgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Xiaoliang Liu

  5. Medical Service, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Yan Su

  6. Department of Pharmacy, Yantai Affiliated Hospital of Binzhou Medical University, No. 717, Jinbu Street, MuPing District, Yantai, 264100, Shandong, China

    Yiwen Gao

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  1. Nan Zhang
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  2. Li Zhao
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  3. Yan Su
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  4. Xiaoliang Liu
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Correspondence to Yiwen Gao.

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11064_2021_3240_MOESM1_ESM.tif

Figure S1. BID overexpression enhanced SK-N-SH and SK-N-BE cell apoptosis. (A) The role of BID overexpression in cell viability was assessed by CCK-8 assay. (B) The role of BID overexpression in cell apoptosis was assessed by flow cytometry assay. (C) The expression of Clwaved-casp3, Bax and Bcl-2 was determined by western blot. **P < 0.01; ANOVA. (TIF 423 kb)

11064_2021_3240_MOESM2_ESM.tif

Figure S2. MiR-124-3p inhibition enhanced SK-N-SH and SK-N-BE cell apoptosis. (A) The role of miR-124-3p inhibition in cell viability was assessed by CCK-8 assay. (B) The role of miR-124-3p inhibition in cell apoptosis was assessed by flow cytometry assay. (C) The expression of Clwaved-casp3, Bax and Bcl-2 was determined by western blot. **P < 0.01; ANOVA. (TIF 434 kb)

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Zhang, N., Zhao, L., Su, Y. et al. Syringin Prevents Aβ25–35-Induced Neurotoxicity in SK-N-SH and SK-N-BE Cells by Modulating miR-124-3p/BID Pathway. Neurochem Res 46, 675–685 (2021). https://doi.org/10.1007/s11064-021-03240-1

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  • DOI: https://doi.org/10.1007/s11064-021-03240-1

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