Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro.
Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro.
复制标题
体外心脏神经嵴细胞同型半胱氨酸反应基因的微阵列分析。
DOI：
10.1002/dvdy.21101
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Finnell,RH
中科院分区：
文献类型：
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作者：
Rosenquist,TH;Bennett,GD;Brauer,PR;Stewart,ML;Chaudoin,TR;Finnell,RH
当叶酸或维生素B12不足时，或在蛋氨酸代谢中重要的酶发生某些突变时，血清中的氨基酸同型半胱氨酸增加。同型半胱氨酸升高与成人心血管疾病和其他疾病的风险增加有关，母体同型半胱氨酸升高会增加某些先天性缺陷的风险，特别是那些由神经嵴和神经管异常发育引起的先天性缺陷。禽类胚胎模型实验表明，同型半胱氨酸升高会干扰神经嵴/神经管在体外和体内的迁移。虽然已经有大量研究表明同型半胱氨酸诱导的成人细胞基因表达变化，但在胚胎神经嵴中没有同型半胱氨酸应答转录组的报道。我们在体外用外源性同型半胱氨酸处理神经嵴细胞，该方案诱导神经嵴细胞迁移的显著变化。我们使用微阵列分析和表达谱来鉴定65个已知功能基因的转录本，这些基因被同型半胱氨酸改变。受影响基因最多的一组（19个）包括那些与细胞迁移和粘附有关的基因。其他主要群体是参与代谢的基因（13）；DNA/RNA相互作用（11）；细胞增殖/凋亡（10）；转运体/受体(6)。虽然在本实验中鉴定的基因与先前观察到的同型半胱氨酸对神经嵴细胞功能的影响一致，但在成人细胞中，没有一个基因被鉴定为对同型半胱氨酸的反应。科学通报，2009,31(2):444 - 444。©2007 Wiley‐Liss, Inc。
The amino acid homocysteine increases in the serum when there is insufficient folic acid or vitamin B12, or with certain mutations in enzymes important in methionine metabolism. Elevated homocysteine is related to increased risk for cardiovascular and other diseases in adults and elevated maternal homocysteine increases the risk for certain congenital defects, especially those that result from abnormal development of the neural crest and neural tube. Experiments with the avian embryo model have shown that elevated homocysteine perturbs neural crest/neural tube migration in vitro and in vivo. Whereas there have been numerous studies of homocysteine‐induced changes in gene expression in adult cells, there is no previous report of a homocysteine‐responsive transcriptome in the embryonic neural crest. We treated neural crest cells in vitro with exogenous homocysteine in a protocol that induces significant changes in neural crest cell migration. We used microarray analysis and expression profiling to identify 65 transcripts of genes of known function that were altered by homocysteine. The largest set of effected genes (19) included those with a role in cell migration and adhesion. Other major groups were genes involved in metabolism (13); DNA/RNA interaction (11); cell proliferation/apoptosis (10); and transporter/receptor (6). Although the genes identified in this experiment were consistent with prior observations of the effect of homocysteine upon neural crest cell function, none had been identified previously as response to homocysteine in adult cells. Developmental Dynamics 236:1044–1054, 2007. © 2007 Wiley‐Liss, Inc.