Ethanol exposure alters protein expression in a mouse model of fetal alcohol spectrum disorders.
Ethanol exposure alters protein expression in a mouse model of fetal alcohol spectrum disorders.
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DOI：
10.1155/2012/867141
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Zhou FC
中科院分区：
文献类型：
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作者：
Mason S;Anthony B;Lai X;Ringham HN;Wang M;Witzmann FA;You JS;Zhou FC
发育期间接触酒精会导致不同程度的生长迟缓和面部畸形，称为胎儿酒精谱系障碍。尽管引起这种疾病的机制还不完全清楚，但最近的进展是酒精诱导了基因表达和胚胎表观基因组的异常变化。为了了解酒精引起的畸形学中的基因和表观遗传学变化，我们使用全胚胎培养来鉴定神经发育中的C6小鼠的酒精签名蛋白质谱。乙醇处理的培养物和对照培养物均质，等电聚焦，并负载进行2D凝胶电泳。染色的凝胶与分析软件进行交叉匹配。我们鉴定了40个差异表达蛋白质点(P<；0.01)，其中9个点用于LC/MS-MS鉴定。免疫分析证实血清转铁蛋白、磷酸丙糖异构酶和泛素结合酶E2 N表达异常。酒精诱导了在细胞功能、细胞周期和泛素-蛋白酶体途径中起作用的蛋白质的改变。几种错误调节的蛋白质与核因子-κB和Myc转录因子级联的效应器相互作用。利用全胚胎培养，我们已经确定了与神经系统发育和功能有关的调控错误的蛋白质。
Alcohol exposure during development can result in variable growth retardation and facial dysmorphology known as fetal alcohol spectrum disorders. Although the mechanisms underlying the disorder are not fully understood, recent progress has been made that alcohol induces aberrant changes in gene expression and in the epigenome of embryos. To inform the gene and epigenetic changes in alcohol-induced teratology, we used whole-embryo culture to identify the alcohol-signature protein profile of neurulating C6 mice. Alcohol-treated and control cultures were homogenized, isoelectrically focused, and loaded for 2D gel electrophoresis. Stained gels were cross matched with analytical software. We identified 40 differentially expressed protein spots (P < 0.01), and 9 spots were selected for LC/MS-MS identification. Misregulated proteins include serotransferrin, triosephosphate isomerase and ubiquitin-conjugating enzyme E2 N. Misregulation of serotransferrin and triosephosphate isomerase was confirmed with immunologic analysis. Alteration of proteins with roles in cellular function, cell cycle, and the ubiquitin-proteasome pathway was induced by alcohol. Several misregulated proteins interact with effectors of the NF-κB and Myc transcription factor cascades. Using a whole-embryo culture, we have identified misregulated proteins known to be involved in nervous system development and function.