Virginia-Maryland Regional College of Veterinary Medicine, 1 Duck Pond Drive, Virginia Tech, Blacksburg, VA, USA.
Neurotoxicology. 2011 Jan;32(1):58-67. doi: 10.1016/j.neuro.2010.10.004. Epub 2010 Oct 21.
The blood-brain barrier (BBB) is essential for central nervous system (CNS) normal function. It is formed by endothelial cells with special characteristics, which confer the BBB with low permeability and high transendothelial electrical resistance (TEER). We previously demonstrated that malathion and lead, two neurotoxicants widely present in the environment, decrease TEER and increase permeability in in vitro models of the BBB. In this study we assessed tight junction disruption at the protein and gene expression levels using a rat brain microvascular endothelial cell line (RBE4) exposed to lead acetate at 10(-5)M and 10(-6)M, malathion at 10(-5)M, malaoxon at 10(-6)M, and their combinations. Cells were incubated with treatments for 2h, 4h, 8h, 16h, and 24h periods. Immunoblotting assessments demonstrated that protein levels of tight junction proteins occludin and claudin 5, and scaffold proteins ZO1 and ZO2 were decreased after treatments. Gene expression determinations did not correlate with the decreases in protein, indicating that the effects on these proteins were post-translational.
血脑屏障 (BBB) 对于中枢神经系统 (CNS) 的正常功能至关重要。它由具有特殊特征的内皮细胞形成，赋予 BBB 低通透性和高跨内皮电阻 (TEER)。我们之前的研究表明，马拉硫磷和铅这两种在环境中广泛存在的神经毒物，会降低体外 BBB 模型中的 TEER 并增加通透性。在这项研究中，我们使用大鼠脑微血管内皮细胞系 (RBE4) 评估了紧密连接在蛋白质和基因表达水平上的破坏，该细胞系暴露于 10(-5)M 和 10(-6)M 的醋酸铅、10(-5)M 的马拉硫磷、10(-6)M 的马拉氧磷及其组合中。细胞用处理物孵育 2h、4h、8h、16h 和 24h。免疫印迹评估表明，紧密连接蛋白 occludin 和 claudin 5 以及支架蛋白 ZO1 和 ZO2 的蛋白水平在处理后降低。基因表达测定与蛋白质的减少不相关，表明这些蛋白质的作用是翻译后修饰。
