PDF(Pubmed)
Abstract：
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a \"first-line\" model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- (PSEN1 and BACE1) and neuroinflammation- (IL-1β and IL-6) associated genes, whereas genes retaining protective roles toward amiloidogenesis were upregulated (ADAM10 and ADAM17). By profiling the DNA methylation patterns of genes known to be epigenetically regulated, we observed a correlation between hypermethylation and the downregulation of PSEN1, IL-1β and IL-6. These results suggest a possible role of MK7R in the treatment of cognitive impairment, giving a possible base for further preclinical experiments in animal models of neurodegenerative disease.
摘要：
除了它在凝血中的作用，维生素K似乎参与了各种其他机制，包括炎症和年龄相关的疾病，也在基因表达水平。这项工作检查了两种维生素K2（甲基萘醌）维生素的作用，即,甲基萘醌-4（MK4）和还原型甲基萘醌-7（MK7R），作为基因调节剂化合物，以及它们在淀粉样蛋白生成和神经炎症相关基因的表观遗传调控中的潜在作用。SK-N-BE人神经母细胞瘤细胞为筛选神经炎症和神经变性分子途径提供了“一线”模型。MK7R,作为一种新的维生素K形式，首先在溶解方面进行了测试，摄取和细胞活力，与MK4一起作为内源性对照。我们评估了淀粉样蛋白生成和神经炎症中关键因素的表达，观察到MK7R治疗与神经变性（PSEN1和BACE1）和神经炎症（IL-1β和IL-6）相关基因的下调有关，而保留对类虫生成保护作用的基因被上调(ADAM10和ADAM17)。通过分析已知受表观遗传调控的基因的DNA甲基化模式，我们观察到甲基化与PSEN1，IL-1β和IL-6的下调之间存在相关性。这些结果表明，MK7R在治疗认知障碍中的可能作用，为神经退行性疾病动物模型的进一步临床前实验提供可能的基础。
