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叶酸缺乏通过增加同型半胱氨酸在体外诱导神经干细胞凋亡。

Folate deficiency induces neural stem cell apoptosis by increasing homocysteine in vitro.

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.

出版信息

J Clin Biochem Nutr. 2009 Jul;45(1):14-9. doi: 10.3164/jcbn.08-223. Epub 2009 Jun 30.

DOI:10.3164/jcbn.08-223
PMID:19590702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2704322/
Abstract

Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays a central role in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In the present study, we investigated the effects of folate deficiency on the cell proliferation, cell apoptosis and homocysteine concentrations in NSCs. NSCs were isolated from fetal rats and identified as NSCs by their expression of immunoreactive nestin. Cell proliferation was quantitated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were detected and confirmed by flow cytometric analysis. We measured homocysteine concentrations in NSCs by high performance liquid chromatography and detected the expression of caspase-3 by western blot method. Folate deficiency not only decreased cell proliferation, but also increased the apoptotic rate of NSCs as demonstrated by the increased expression of early apoptotic markers such as caspase-3, compared to control group (p<0.05). Furthermore, There was a statistically significant increase in homocysteine concentration during folate deficiency in NSCs (p<0.05). These data suggest that folate affects the cell proliferation, apoptosis and homocysteine generation in NSC cells.

摘要

神经祖细胞的细胞事件,如增殖和分化,受多种内在和外在细胞信号的调节。叶酸在中枢神经系统发育中起着核心作用,因此作为外在信号的叶酸可能会影响神经干细胞(NSC)的增殖和分化。在本研究中,我们研究了叶酸缺乏对 NSCs 细胞增殖、细胞凋亡和同型半胱氨酸浓度的影响。NSCs 从胎鼠中分离出来,并通过其免疫反应性巢蛋白的表达来鉴定为 NSCs。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法定量细胞增殖。通过流式细胞术分析检测和确认凋亡细胞。我们通过高效液相色谱法测量 NSCs 中的同型半胱氨酸浓度,并通过 Western blot 法检测 caspase-3 的表达。与对照组相比(p<0.05),叶酸缺乏不仅降低了 NSCs 的细胞增殖,还增加了 NSCs 的凋亡率,这表现为早期凋亡标志物如 caspase-3 的表达增加。此外,在 NSCs 中叶酸缺乏时同型半胱氨酸浓度呈统计学显著增加(p<0.05)。这些数据表明,叶酸影响 NSC 细胞的细胞增殖、凋亡和同型半胱氨酸生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/7825bc6c3b61/jcbn08-223f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/6acd72499e6f/jcbn08-223f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/dc14578f2943/jcbn08-223f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/c75dd51a3536/jcbn08-223f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/ba6a44239b79/jcbn08-223f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/7825bc6c3b61/jcbn08-223f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/6acd72499e6f/jcbn08-223f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/dc14578f2943/jcbn08-223f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/c75dd51a3536/jcbn08-223f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/ba6a44239b79/jcbn08-223f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d633/2704322/7825bc6c3b61/jcbn08-223f05.jpg

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