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Berberine attenuates Aβ42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.
Life Sciences ( IF 5.2 ) Pub Date : 2020-04-03 , DOI: 10.1016/j.lfs.2020.117637
Nan Zhang 1 , Yiwen Gao 2 , Shaoli Yu 3 , Xiaohong Sun 2 , Ke Shen 4
Affiliation  

BACKGROUND Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD. METHODS Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residue β-amyloid (Aβ42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aβ42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aβ42-treated HN cells. Berberine alleviated Aβ42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aβ42-induced HN cell neurotoxicity via miR-142-5p. CONCLUSION Our current study suggested that berberine protected HN cell from Aβ42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.

中文翻译:

小ber碱通过调节人神经元细胞中的circHDAC9 / miR-142-5p轴来减轻Aβ42诱导的神经元损伤。

背景技术小ber碱在神经退行性疾病包括阿尔茨海默氏病(AD)中起神经保护作用。环状RNA(circRNA)在AD发病机理中起着至关重要的作用。在当前的工作中,我们旨在调查circRNA组蛋白脱乙酰基酶9(circHDAC9)是否参与AD中小ber碱的调节。方法分别通过细胞计数试剂盒8(CCK-8)和流式细胞仪测定细胞活力和凋亡。酶联免疫吸附试验(ELISA)用于评估caspase-3活性以及白介素-1β(IL-1β),IL-6和肿瘤坏死因子-α(TNF-α)的产生。通过定量实时聚合酶链反应(qRT-PCR)检测circHDAC9和miR-142-5p的水平。进行亚细胞分级测定以评估circHDAC9的定位。双重荧光素酶报道分子,RNA免疫沉淀(RIP)和RNA下拉实验证实了circHDAC9与miR-142-5p之间的直接相互作用。结果我们的数据表明,circHDAC9确实是环状转录本,并且主要位于细胞质中。42个残基的β-淀粉样蛋白(Aβ42)在人神经元(HN)细胞中触发了circHDAC9的显着下调和miR-142-5p的显着上调。小ber碱缓解Aβ42诱导的HN细胞神经毒性。此外,小ber碱在Aβ42处理的HN细胞中导致circHDAC9表达增加,而miR-142-5p水平降低。小ber碱通过上调circHDAC9减轻HN细胞中Aβ42诱导的神经元损伤。此外,circHDAC9充当miR-142-5p的分子海绵。CircHDAC9过表达通过miR-142-5p减轻了Aβ42诱导的HN细胞神经毒性。
更新日期:2020-04-06
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