title: DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.
abstract: 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 μmol/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 μmol/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.
authors: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors: Wen
authors: W
authors: Li
authors: Min
authors: M
authors: Yu
authors: Suhui
authors: S
authors: Luo
authors: Huan
authors: H
authors: Liu
authors: Yuxia
authors: Y
authors: Gao
authors: John X
authors: JX
authors: Wilson
authors: Guowei
authors: G
authors: Huang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005492:Folic Acid; D015254:DNA Modification Methylases