Ethanol inhibits neural cell-cell adhesion.
Ethanol inhibits neural cell-cell adhesion.
复制标题
DOI：
10.1016/s0021-9258(17)37108-9
复制
发表时间：
1994-03
期刊：
影响因子：
--
通讯作者：
Michael E. CharnessSJn;Rebecca M. SafranO;George Peridesll
中科院分区：
文献类型：
--
作者：
Michael E. CharnessSJn;Rebecca M. SafranO;George Peridesll
妊娠期暴露于乙醇会导致神经元迁移、束化和突触发生的缺陷，这些发育事件依赖于细胞粘附分子（CAMs）的模式表达和功能。重组人成骨蛋白1 （hOP-1）通过强烈诱导N-CAM和L1，在增殖的神经母细胞瘤与胶质瘤杂交细胞NG108-15中增加细胞间的粘附，促进细胞聚集。本研究表明，在社交饮酒过程中获得的乙醇浓度抑制了hop -1诱导的细胞聚集，但不影响细胞增殖、N-CAM和L1的诱导和细胞表面表达，也不影响N-CAM的选择性剪接和唾液化。这种抑制作用可由其他醇按其链长的比例再现，但不能由致畸抗惊厥药或苯丙氨酸再现。乙醇对hOP-1形态发生的抑制作用与hOP-1的浓度成反比，因此与N-CAM和L1的水平成反比。低浓度乙醇（IC50为5 ~ 10 mM）抑制了hop -1处理细胞的细胞粘附，丙醇和丁醇也能更有效地复制这种作用。乙醇可能通过抑制cam介导的细胞间相互作用而扰乱大脑和骨骼发育。
Gestational exposure to ethanol causes defects in neuronal migration, fasciculation, and synaptogenesis, developmental events that depend on the patterned expression and function of cell adhesion molecules (CAMs). Recombinant human osteogenic protein-1 (hOP-1) increases cell-cell adhesion and promotes cell clustering in proliferating neuroblastoma x glioma hybrid NG108-15 cells by strongly inducing N-CAM and L1. Here we show that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N-CAM. This inhibition was reproduced by other alcohols in proportion to their chain length, but not by teratogenic anticonvulsants or phenylalanine. Ethanol inhibition of hOP-1 morphogenesis was inversely proportional to the concentration of hOP-1 and, hence, to the levels of N-CAM and L1. Low concentrations of ethanol (IC50 5-10 mM) inhibited cell-cell adhesion in hOP-1-treated cells, and this action too was reproduced more potently by propanol and butanol. Ethanol may perturb brain and skeletal development by inhibiting CAM-mediated cell-cell interactions.