Gubitosi-Klug Rose, Larimer Corena G, Bearer Cynthia F
Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106-6010, USA.
Neurotoxicology. 2007 May;28(3):457-62. doi: 10.1016/j.neuro.2006.11.008. Epub 2006 Dec 2.
L1 cell adhesion molecule (L1), a protein critical for appropriate development of the central nervous system, is a target for ethanol teratogenicity. Ethanol inhibits both L1 mediated cell adhesion as well as L1 mediated neurite outgrowth. L1 has been shown to increase cell survival in cerebellar granule cells while ethanol has been shown to increase cell death. We sought to determine if L1 protected cells from ethanol induced cell death. Cerebellar granule cells from postnatal day 6 rat pups were cultured on either poly l-lysine with or without an L1 substratum. Alcohol was added at 2h post-plating and cell survival was measured at various times. L1 substratum significantly increased cell survival at 72 and 120 h. Ethanol significantly reduced cell survival at 48 h, with no effect at 72 or 120 h, both in the presence and absence of L1. At 48 h, L1 significantly increased cell survival in the presence of ethanol. We conclude that ethanol interferes with processes other than L1-L1 interactions in causing cell death, and that ethanol effects would be more severe in the absence of L1.
L1细胞粘附分子(L1)是一种对中枢神经系统正常发育至关重要的蛋白质,是乙醇致畸作用的靶点。乙醇既抑制L1介导的细胞粘附,也抑制L1介导的神经突生长。已表明L1可增加小脑颗粒细胞的细胞存活率,而乙醇则可增加细胞死亡。我们试图确定L1是否能保护细胞免受乙醇诱导的细胞死亡。将出生后第6天的大鼠幼崽的小脑颗粒细胞培养在有或没有L1基质的聚L-赖氨酸上。接种后2小时加入酒精,并在不同时间测量细胞存活率。L1基质在72小时和120小时时显著提高了细胞存活率。在有和没有L1的情况下,乙醇在48小时时显著降低了细胞存活率,而在第72或120小时时没有影响。在48小时时,L1在有乙醇存在的情况下显著提高了细胞存活率。我们得出结论,乙醇在导致细胞死亡时干扰了L1-L1相互作用以外的其他过程,并且在没有L1的情况下乙醇的影响会更严重。