Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky, Lexington, KY 40536.
Environ Toxicol Pharmacol. 2008 Mar;25(2):234-40. doi: 10.1016/j.etap.2007.10.019.
Polychlorinated biphenyl (PCB) congeners exhibit a broad range of adverse biological effects including neurotoxicity. The mechanisms by which PCBs cause neurotoxic effects are still not completely understood. The blood-brain barrier (BBB) is a physical and metabolic barrier separating brain microenvironment from the peripheral circulation and is mainly composed of endothelial cells connected by tight junctions. We examined the effects of several highly-chlorinated PCB congeners on expression of tight junction proteins in human brain endothelial cells. Treatment for 24 h with selective PCB congeners disrupted expression of the cytosolic scaffold proteins of tight junctions, such as zonula occludens (ZO)-1, ZO-2, and AF6. In contrast, PCB exposure did not alter expression of integral membrane proteins, junctional adhesion molecule-A (JAM-A), and claudin-1. Based on these data, we suggest that PCB-mediated selective alterations of tight junction protein expression may contribute to their neurotoxic effects in the central nervous system.
多氯联苯 (PCB) 同系物表现出广泛的不良生物学效应,包括神经毒性。PCBs 引起神经毒性效应的机制仍不完全清楚。血脑屏障 (BBB) 是一种物理和代谢屏障,将脑微环境与外周循环分开,主要由通过紧密连接连接的内皮细胞组成。我们研究了几种高氯化 PCB 同系物对人脑血管内皮细胞中紧密连接蛋白表达的影响。用选择性 PCB 同系物处理 24 小时会破坏紧密连接的细胞质支架蛋白的表达,如封闭蛋白 (ZO)-1、ZO-2 和 AF6。相比之下,PCB 暴露不会改变整合膜蛋白、连接黏附分子-A (JAM-A) 和 Claudin-1 的表达。基于这些数据,我们认为 PCB 介导的紧密连接蛋白表达的选择性改变可能有助于它们在中枢神经系统中的神经毒性作用。