Toborek M, Barger S W, Mattson M P, Espandiari P, Robertson L W, Hennig B
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054, USA.
J Biochem Toxicol. 1995 Aug;10(4):219-26. doi: 10.1002/jbt.2570100406.
Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery-derived endothelial cells were exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,4,4',5-pentachlorobiphenyl (PCB 114), or 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 and PCB 114 significantly disrupted, in a dose-dependent manner, endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. These PCBs also contributed markedly to cellular oxidative stress, as measured by 2,7-dichlorofluorescin (DCF) fluorescence and lipid hydroperoxides, and caused a significant increase in intracellular calcium ([Ca2+]i) levels. Enhanced oxidative stress and [Ca2+]i in PCB 77- and PCB 114-treated cells were accompanied by increased activity and content of cytochrome P450 1A and by a decrease in the vitamin E content in the culture medium. In contrast to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no effect on cellular oxidation, [Ca2+]i, or endothelial barrier function. These results suggest that certain PCBs may play a role in the development of atherosclerosis by causing endothelial cell dysfunction and a decrease in the barrier function of the vascular endothelium. It is possible that interaction of PCBs with the Ah receptor and activation of the cytochrome P450 1A subfamily are involved in this pathology.
环境化学物质，如多氯联苯（PCBs），可能通过破坏血管内皮的正常功能而具有致动脉粥样硬化作用。为了研究这一假说，将猪肺动脉来源的内皮细胞暴露于3,3',4,4'-四氯联苯（PCB 77）、2,3,4,4',5-五氯联苯（PCB 114）或2,2',4,4',5,5'-六氯联苯（PCB 153）中长达24小时。选择这些多氯联苯是因为它们与芳烃（Ah）受体的结合亲和力不同以及它们诱导细胞色素P450的差异。PCB 77和PCB 114以剂量依赖的方式显著破坏内皮屏障功能，使白蛋白跨内皮单层的转运增加。这些多氯联苯还显著导致细胞氧化应激，通过2,7-二氯荧光素（DCF）荧光和脂质氢过氧化物测定，并导致细胞内钙（[Ca2+]i）水平显著升高。PCB 77和PCB 114处理的细胞中氧化应激增强和[Ca2+]i升高伴随着细胞色素P450 1A的活性和含量增加以及培养基中维生素E含量降低。与PCB 77和PCB 114的作用相反，细胞暴露于PCB 153对细胞氧化、[Ca2+]i或内皮屏障功能没有影响。这些结果表明，某些多氯联苯可能通过导致内皮细胞功能障碍和血管内皮屏障功能降低而在动脉粥样硬化的发展中起作用。多氯联苯与Ah受体的相互作用以及细胞色素P450 1A亚家族的激活可能参与了这一病理过程。
