ALCOHOL AND CELL ADHESION

描述：（改编自研究者摘要）乙醇抑制细胞 在神经细胞中由L1细胞粘附分子介导的粘附， 用人L1转染的成纤维细胞。因为L1儿童的大脑 突变类似于患有胎儿酒精综合征的儿童， L1介导的细胞粘附的抑制可能有助于 ETOH的致畸作用。一系列的结构活性分析 直链和支链醇显示出显著的结构 对酒精抑制细胞-细胞粘附的特异性。而且我们 确定了一系列化合物，拮抗乙醇对 L1介导的细胞-细胞粘附，对培养的神经细胞中BMP形态发生的影响， 以及小鼠全胚胎培养物的发育。底层 该建议的假设是，拮抗乙醇的化合物 抑制L1介导的细胞-细胞粘附也将拮抗乙醇 致畸作用本研究有三个具体目标：1。以识别 所需的醇类和相关化合物的结构决定因素 用于抑制表达L1的细胞中的细胞-细胞粘附和用于拮抗 这种抑制; 2。为了表征L1的区域， 乙醇抑制和乙醇抑制的拮抗作用; 3.评价 选择性乙醇拮抗剂，因为它们能够防止致畸性 乙醇对小鼠全胚胎培养及早期胚胎发育的影响 C57 BL/6 J小鼠。这些研究中采用的技术将包括哺乳动物 细胞转染，细胞聚集测定，L1分子的诱变， 小鼠全胚胎培养，以及小鼠的肉眼和显微镜分析 在子宫内接触乙醇这些实验可能会导致更好的 了解乙醇如何与神经蛋白相互作用，并可能揭示 乙醇导致出生缺陷的机制。拟议的一个主要目标是 研究的目的是确定化合物，减少致畸作用的 乙醇

DESCRIPTION: (Adapted from the Investigator’s Abstract) Ethanol inhibits cell adhesion mediated by the L1 cell adhesion molecule in neural cells and fibroblasts transfected with human L1. Because the brains of children with L1 mutations resemble those of children with fetal alcohol syndrome, it is possible that inhibition of L1-mediated cell adhesion contributes to the teratogenic effects of ETOH. Structure activity analysis of a series of straight and branch-chain alcohols demonstrates remarkable structural specificity for alcohol inhibition of cell-cell adhesion. Moreover, we have identified a series of compounds that antagonize the effects of ethanol on L1-mediated cell-cell adhesion, on BMP morphogenesis in cultured neural cells, and on the development of mouse whole embryo cultures. The underlying hypothesis of this proposal is that compounds that antagonize ethanol inhibition of L1-mediated cell-cell adhesion will also antagonize ethanol teratogenesis. The proposed research has three specific aims: 1. To identify the structural determinants of alcohols and related compounds that are required for inhibition of cell-cell adhesion in L1-expressing cells and for antagonism of this inhibition; 2. To characterize regions of L1 that are necessary for alcohol inhibition and for antagonism of ethanol inhibition; 3. To evaluate selective ethanol antagonists for their ability to prevent the teratogenic effects of ethanol in mouse whole embryo culture and during early embryogenesis in C57BL/6J mice. Techniques employed in these studies will include mammalian cell transfection, cell-aggregation assays, mutagenesis of the L1 molecule, mouse whole embryo culture, and macroscopic and microscopic analysis of mice exposed to ethanol in utero. These experiments may lead to a better understanding of how ethanol interacts with neural proteins and may reveal mechanisms whereby ethanol causes birth defects. A major goal of the proposed research is to identify compounds that reduce the teratogenic effects of ethanol.