DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate
DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate
复制标题
DNA甲基转移酶介导叶酸对神经干细胞增殖的剂量依赖性刺激
DOI：
10.1016/j.jnutbio.2012.11.001
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Huang, Guowei
中科院分区：
文献类型：
--
作者：
Li, Wen;Yu, Min;Huang, Guowei
神经干细胞对叶酸的增殖反应可能在中枢神经系统的发育、功能和修复中起关键作用。重要的是确定叶酸在NSC培养物中的剂量依赖性作用，NSC培养物是用于治疗神经退行性疾病的可移植细胞的潜在来源。为了确定叶酸在体外刺激NSC增殖的最佳浓度和作用机制，将NSC暴露于叶酸或5-甲基四氢叶酸（5-MTHF）（0-200 μ mol/L）24、48或72 h。免疫细胞化学和四甲基偶氮唑蓝法显示，叶酸对神经干细胞增殖的最适浓度为20-40 μ mol/L。叶酸对NSC增殖的刺激与DNA甲基转移酶（DNMT）激活相关，并被DNMT抑制剂zebularine减弱，这意味着叶酸通过DNMT依赖性机制剂量依赖性地刺激NSC增殖。基于这些新发现和先前发表的证据，我们已经确定了叶酸刺激NSC生长的机制。(C)2013 Elsevier Inc. All rights reserved.
The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 mu mol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 mu mol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. (C) 2013 Elsevier Inc. All rights reserved.