Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells.
Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells.
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DOI：
10.3390/ijms161025002
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发表时间：
2015-10-20
影响因子：
5.6
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Li W;Jiang M;Zhao S;Liu H;Zhang X;Wilson JX;Huang G
阿尔茨海默病(AD)是一种导致进行性痴呆的常见神经退行性疾病，也是老年人痴呆的主要原因。叶酸通过一碳代谢来支持多种底物的甲基化。我们推测，补充叶酸可以调节DNA甲基转移酶(DNMT)的活性，并可能改变AD患者淀粉样蛋白β肽(Aβ)的产生。将表达人APP695的小鼠神经2a细胞与叶酸(2.8~40μ/L)孵育，并分别加入或不加入去甲基四氢叶酸(DNMT)抑制剂ZeBularine。检测DNMT活性、细胞存活率、Aβ和DNMT表达。结果表明，叶酸可促进DNMT基因和蛋白的表达，提高DNMT的活性。此外，叶酸降低了Aβ蛋白的产量，而ZeBularine抑制DNMT活性增加了Aβ的产量。结果表明，叶酸诱导甲基化潜能依赖的DNMT酶，从而抑制Aβ的产生。
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.