Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells
Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells
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DOI：
10.1074/jbc.274.19.13264
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发表时间：
1999-05-07
影响因子：
4.8
通讯作者：
Cheng, GH
中科院分区：
文献类型：
--
作者：
Bearer, CF;Swick, AR;Cheng, GH
乙醇对发育中的中枢神经系统的影响的神经病理学与神经细胞粘附分子L1突变的患者相似。这一观察结果表明，抑制L1在酒精相关的神经发育障碍的发病机制中发挥作用。在这里，我们研究了乙醇对L1血友病结合和L1介导的神经突生长的影响。在表达全长人L1的骨髓瘤细胞系中，乙醇对细胞粘附或聚集没有影响。相比之下，L1介导的神经突起生长率的大鼠出生后第6天小脑颗粒细胞生长的Ng-CAM，鸡同源的L1，抑制了48.6%，在乙醇的存在下，半最大浓度为4.7 mM，相同的效果被发现与可溶性L1-Fc，从而表明，抑制作用是不依赖于细胞粘附。与此相反，无论是层粘连蛋白，也不N-钙粘蛋白介导的神经突起生长抑制生理浓度的乙醇。我们的结论是，乙醇的毒性发育中枢神经系统的机制之一可能是抑制L1介导的神经突起生长。
The neuropathology of the effects of ethanol on the developing central nervous system are similar to those of patients with mutations in L1, a neural cell adhesion molecule. This observation suggests that inhibition of L1 plays a role in the pathogenesis of alcohol-related neurodevelopmental disorders. Here we examine the effects of ethanol on L1 hemophilic binding and on L1 mediated neurite outgrowth. Ethanol had no effect on cell adhesion or aggregation in a myeloma cell line expressing full-length human L1. In contrast, the rate of L1-mediated neurite outgrowth of rat postnatal day 6 cerebellar granule cells grown on a substratum of Ng-CAM, the chick homologue of L1, was inhibited by 48.6% in the presence of ethanol with a half-maximal concentration of 4.7 mM, The same effect was found with soluble L1-Fc, thus showing that the inhibitory effect is not dependent on cell adhesion. In contrast, neither laminin nor N-cadherin-mediated neurite outgrowth was inhibited by physiologic concentrations of ethanol. We conclude that one mechanism of ethanol's toxicity to the developing central nervous system may be the inhibition of L1-mediated neurite outgrowth.