Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose
Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose
复制标题
叶酸补充影响高糖环境下胚胎神经干细胞的凋亡和分化
DOI：
10.1016/j.neulet.2008.05.053
复制
发表时间：
2008-07-25
影响因子：
2.5
通讯作者：
Hao, Ai-Jun
中科院分区：
文献类型：
--
作者：
Jia, De-Yong;Liu, Hui-Juan;Hao, Ai-Jun
叶酸（FA）补充剂已被证明在减少神经管缺陷（NTD）的发生方面非常有效，NTD是与糖尿病妊娠相关的最常见的出生缺陷之一。然而，FA在糖尿病诱导的NTDs中的抗致畸机制尚不清楚。本研究探讨了FA对高糖环境下神经干细胞的保护作用机制。将未分化和分化的神经干细胞分别在正常葡萄糖浓度（NG）和高糖浓度（HG）下培养，并加入或不加入FA。补充FA可显著降低HG诱导的神经干细胞凋亡，并降低HG诱导的未分化神经干细胞核中p53的表达。在分化的神经干细胞中给予FA并不能改变HG诱导的神经干细胞的早熟分化。在HG存在下，FA对碱性螺旋-环-螺旋因子包括Neurog 1、Neurog 2、NeuroD 2、Mash 1、Id 1、Id 2和Hes 5的mRNA表达水平的增加没有显著影响。本研究结果提供了一种细胞机制，通过该机制，FA补充可能在预防糖尿病妊娠NTD中具有潜在作用。另一方面，FA增加了上述转录因子的mRNA表达水平，加速了NSCs在NG培养基中的分化，提示FA可能对NSCs的正常分化产生不利影响。因此，FA的时机和剂量将是考虑在正常妊娠的母亲补充FA的关键因素。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Folic acid (FA) supplementation has been shown to be extremely effective in reducing the occurrence of neural tube defects (NTDs), one of the most common birth defects associated with diabetic pregnancy. However, the antiteratogenic mechanism of FA in diabetes-induced NTDs is unclear. This study investigated the neuroprotective mechanism of FA in neural stem cells (NSCs) exposed to high glucose in vitro. The undifferentiated or differentiated NSCs were cultured in normal D-glucose concentration (NG) or high D-glucose concentration (HG) with or without FA. FA supplementation significantly decreased apoptosis induced by HG and lowered the expression of p53 in the nucleus of undifferentiated NSCs exposed to HG. Administration of FA in differentiated NSCs did not alter their precocious differentiation induced by HG. The increased mRNA expression levels of the basic helix-loop-helix factors including Neurog1, Neurog2, NeuroD2, Mash1, Id1, Id2, and Hes5 in the presence of HG were not significantly affected by FA. The present results provided a cellular mechanism by which FA supplementation may have a potential role in prevention of NTDs in diabetic pregnancies. On the other hand, FA increased the mRNA expression levels of the above transcription factors and accelerated the differentiation of NSCs in the NG medium, suggesting that it may adversely affect the normal differentiation of NSCs. Therefore, the timing and dose of FA would be critical factors in considering FA supplementation in normal maternal pregnancy. (C) 2008 Elsevier Ireland Ltd. All rights reserved.