Zhang Yanchun, Chen Deqiang, Tian Rui, Yan Xinyue, Zhou Yingwen
Department of Rehabilitation, Cangzhou Central Hospital, Cangzhou, China.
Department of CT Room, Cangzhou Central Hospital, Cangzhou, China.
Chem Biol Drug Des. 2023 Nov;102(5):1121-1132. doi: 10.1111/cbdd.14313. Epub 2023 Aug 24.
Resveratrol (Res) has been identified to reduce neurodegeneration. Circular RNAs (circRNAs) are stable noncoding RNAs that are considered to be ideal biomarkers for molecular targeting treatment. Here, this study focused on investigating the function and relationship of circ_0050263 and Res in Alzheimer's Disease (AD). Human neuroblastoma cell line SK-N-SH was exposed to amyloid-β (Aβ) to induce AD cell model in vitro. Cell viability, apoptosis, and inflammatory reaction were evaluated by CCK-8 assay, flow cytometery, and ELISA analysis. The oxidative stress and endoplasmic reticulum stress (ERS) were determined by detecting related markers. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter assay was adopted to verify the binding between miR-361-3p and circ_0050263 or PDE4A (Phosphodiesterase 4A). Subsequently, we found that Res treatment alleviated Aβ-induced apoptosis, inflammatory response, oxidative stress, and ERS in SK-N-SH cells. Circ_0050263 is a stable circRNA, which was increased by Aβ, but decreased by Res in SK-N-SH cells. Circ_0050263 overexpression reversed Res-induced neuroprotective effects. Mechanistically, circ_0050263 acted as a sponge for miR-361-3p, which targeted PDE4A. Circ_0050263 silencing abated Aβ-induced neuronal injury, which were counteracted by following PDE4A overexpression. Moreover, PDE4A upregulation could attenuate Res-mediated neuroprotective effects. In all, Res alleviated Aβ-induced neuronal apoptosis, inflammation, oxidative stress, and ERS via circ_0050263/miR-361-3p/PDE4A axis, providing new insights for AD therapy.
白藜芦醇（Res）已被证实可减少神经退行性变。环状RNA（circRNAs）是稳定的非编码RNA，被认为是分子靶向治疗的理想生物标志物。在此，本研究聚焦于探究circ_0050263与Res在阿尔茨海默病（AD）中的作用及关系。将人神经母细胞瘤细胞系SK-N-SH暴露于淀粉样β蛋白（Aβ）以在体外诱导AD细胞模型。通过CCK-8检测、流式细胞术和ELISA分析评估细胞活力、凋亡和炎症反应。通过检测相关标志物来确定氧化应激和内质网应激（ERS）。采用qRT-PCR和蛋白质免疫印迹法检测基因和蛋白质水平。采用双荧光素酶报告基因检测法验证miR-361-3p与circ_0050263或磷酸二酯酶4A（PDE4A）之间的结合。随后，我们发现Res处理可减轻Aβ诱导的SK-N-SH细胞凋亡、炎症反应、氧化应激和ERS。Circ_0050263是一种稳定的circRNA，在SK-N-SH细胞中被Aβ上调，但被Res下调。Circ_0050263过表达逆转了Res诱导的神经保护作用。机制上，circ_0050263作为miR-361-3p的海绵，而miR-361-3p靶向PDE4A。Circ_0050263沉默减轻了Aβ诱导的神经元损伤，随后PDE4A过表达可抵消这种损伤。此外，PDE4A上调可减弱Res介导的神经保护作用。总之，Res通过circ_0050263/miR-361-3p/PDE4A轴减轻了Aβ诱导的神经元凋亡、炎症、氧化应激和ERS，为AD治疗提供了新的见解。
