DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate

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• 作者：Wen Li^a ; ¹ ; Min Yu^a ; ¹ ; Suhui Luo^a ; Huan Liu^a ; Yuxia Gao^b ; John X. Wilson^c ; Guowei Huang^a ; ^{huangguowei@tijmu.edu.cn}
• 关键词：5-MTHF ; 5-methyltetrahydrofolate ; AdoMet ; S-adenosylmethionine ; bFGF ; basic fibroblast growth factor ; BrdU ; 5-bromo-20-deoxyuridine ; CNS ; central nervous system ; DNMT ; DNA methyltransferase ; DMEM ; Dulbecco's modified Eagle's medium ; EGF ; epidermal growth
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：24
• 期：7
• 页码：1295-1301
• 全文大小：2261 K

文摘

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 ¦Ìmol/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 ¦Ìmol/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.