Li Wen, Jiang Mingyue, Zhao Shijing, Liu Huan, Zhang Xumei, Wilson John X, Huang Guowei
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA.
Int J Mol Sci. 2015 Oct 20;16(10):25002-13. doi: 10.3390/ijms161025002.
Alzheimer's disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8-40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，可导致进行性痴呆，是老年人痴呆的主要原因。叶酸通过一碳代谢作用来支持多种底物的甲基化。我们推测补充叶酸可调节DNA甲基转移酶（DNMT）活性，并可能改变AD中淀粉样β肽（Aβ）的产生。将表达人APP695的小鼠Neuro-2a细胞与叶酸（2.8 - 40 μmol/L）一起孵育，同时添加或不添加zebularine（DNMT抑制剂）。然后检测DNMT活性、细胞活力、Aβ和DNMTs表达。结果表明，叶酸刺激了DNMT基因和蛋白表达以及DNMT活性。此外，叶酸降低了Aβ蛋白的产生，而zebularine对DNMT活性的抑制则增加了Aβ的产生。结果表明，叶酸诱导甲基化潜能依赖性DNMT酶，从而减弱Aβ的产生。
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