Loss of arginase I results in increased proliferation of neural stem cells
Loss of arginase I results in increased proliferation of neural stem cells
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DOI：
10.1002/jnr.20964
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发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Yer, Ramaswamy K.
中科院分区：
文献类型：
--
作者：
Becker-Catania, Sara G.;Gregory, Teresa L.;Yer, Ramaswamy K.
脱氢酶I（AI）的缺失导致代谢紊乱，其特征为生长迟缓、精神损害和痉挛增加以及潜在的致命性高氨血症。这种综合征加上越来越多的证据支持精氨酸酶和精氨酸代谢物在正常神经元发育和功能中的作用。在这里，我们报告我们的初步观察AI损失的影响，从胚胎和新生儿AI敲除（KO）小鼠的生发区分离的神经干细胞（NSC）的增殖和分化与杂合子（HET）和野生型（WT）对照动物相比。通过使用短期和长期增殖试验（分别为3天和10天），我们发现KO细胞的数量比WT增加了1.5-2倍，FACS分析显示KO细胞在细胞周期的合成期比WT细胞增加。在NSC分化后，AI缺陷细胞表达β-微管蛋白、SM 181（SNAP 25）、胶质细胞酸性蛋白和CNY，其是与神经元、星形胶质细胞和少突胶质细胞一致的标志物。许多KO细胞表现出更成熟的形态，并表达HET或WT细胞中减少或不存在的成熟神经元标志物。有限的比较表达阵列和定量RTPCR分析鉴定了KO和WT细胞之间编码结构、信号传导和精氨酸代谢蛋白的几种mRNA水平的差异。这些变化的结果可能导致KO与WT细胞的表型差异。AI可能在神经干细胞的生长发育中发挥重要的和意想不到的作用。(c)2006威利-利斯公司
Loss of arginase I (AI) results in a metabolic disorder characterized by growth retardation, increased mental impairment and spasticity, and potentially fatal hyperammonemia. This syndrome plus a growing body of evidence supports a role for arginase and arginine metabolites in normal neuronal development and function. Here we report our initial observations of the effects of AI loss on proliferation and differentiation of neural stem cells (NSCs) isolated from the germinal zones of embryonic and newborn AI knockout (KO) mice compared with heterozygous (HET) and wild-type (WT) control animals. By using both short and long-term proliferation assays (3 and 10 days, respectively), we found a 1.5-2-fold increase in the number of KO cells compared with WT FACS analysis showed an increase in KO cells in the synthesis phase of the cell cycle vs. WT cells. After NSC differentiation, AI-deficient cells expressed beta-tubulin, SM181 (SNAP25), glial fibrillary acidic protein, and CNPase, which are markers consistent with neurons, astrocytes, and oligodendrocytes. Many KO cells exhibited a more mature morphology and expressed mature neuronal markers that were decreased or not present in HET or WT cells. Limited, comparative expression array and quantitative RTPCR analysis identified differences in the levels of several mRNAs encoding structural, signaling, and arginine metabolism proteins between KO and WT cells. The consequence of these changes may contribute to the differential phenotypes of KO vs. WT cells. It appears that AI may play an important and unanticipated role in growth and development of NSCs. (c) 2006 Wiley-Liss, Inc.