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Effects of Zinc and DHA on the Epigenetic Regulation of Human Neuronal Cells

机译:锌和DHA对人神经元细胞表观遗传调控的影响

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Dietary intake of zinc and omega-3 fatty acids (DHA) have health benefits for a number of human diseases. However, the molecular basis of these health benefits remains unclear. Recently, we reported that zinc and DHA affect expression levels of histones H3 and H4 in human neuronal M17 cells. Here, using immunoblotting and densitometric analysis, we aimed to investigate the effect of zinc and DHA on post-translational modifications of histone H3 in M17 cells. In response to increase in zinc concentration, we observed increase in deacetylation, methylation and phosphorylation of H3 and decrease in acetylation. We also investigated the role of zinc in apoptosis, and found that zinc reduced the levels of the anti-apoptotic marker Bcl-2 while increasing the apoptotic marker caspase-3 levels, correlating with cell viability assays. Conversely, DHA treatment resulted in increase in acetylation of H3 and Bcl-2 levels and decrease in deacetylation, methylation, phosphorylation of H3 and caspase-3 levels, suggesting that DHA promotes gene expression and neuroprotection. Our novel findings show the opposing effects of zinc and DHA on the epigenetic regulation of human neuronal cells and highlight the potential benefit of dietary intake of DHA for management of neurodegenerative diseases.
机译:饮食中锌和omega-3脂肪酸(DHA)的饮食对许多人类疾病都有健康益处。但是,这些健康益处的分子基础仍然不清楚。最近,我们报道锌和DHA影响人神经元M17细胞中组蛋白H3和H4的表达水平。在这里,我们使用免疫印迹和光密度分析,旨在研究锌和DHA对M17细胞中组蛋白H3的翻译后修饰的影响。为了响应锌浓度的增加,我们观察到H3的脱乙酰基,甲基化和磷酸化增加,而乙酰化降低。我们还研究了锌在细胞凋亡中的作用,并发现锌降低了抗凋亡标记物Bcl-2的水平,同时增加了凋亡标记物caspase-3的水平,与细胞活力测定相关。相反,DHA处理导致H3和Bcl-2水平的乙酰化增加,而H3和caspase-3水平的脱乙酰基,甲基化,磷酸化降低,表明DHA促进基因表达和神经保护。我们的新发现显示锌和DHA对人类神经元细胞的表观遗传调控的相反作用,并突出显示饮食中摄入DHA对管理神经退行性疾病的潜在益处。

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