Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington, KY, 40536.
Environ Toxicol Pharmacol. 2008 Mar;25(2):197-201. doi: 10.1016/j.etap.2007.10.016.
Zinc has anti-inflammatory properties and is crucial for the integrity of vascular endothelial cells, and the development and homeostasis of the cardiovascular system. The aryl hydrocarbon receptor (AhR) which is expressed in the vascular endothelium also plays an important role in responses to xenobiotic exposure and cardiovascular development. We hypothesize that cellular zinc can modulate induction of AhR responsive genes in endothelial cells. To determine if zinc deficiency can alter responses to AhR ligands, aortic endothelial cells were exposed to the AhR ligands 3,3',4,4'-tetrachlorobiphenyl (PCB77) or beta-naphthoflavone (beta-NF) alone or in combination with the membrane permeable zinc chelator TPEN, followed by measurements of the AhR responsive cytochrome P450 enzymes CYP1A1 and 1B1. Compared to vehicle treated cells, both PCB77-induced CYP1A1 activity (EROD) and mRNA expression were significantly reduced during zinc deficiency. In addition, PCB77 and beta-NF-mediated upregulation of CYP1A1 and CYP1B1 protein expression was significantly reduced in zinc-deficient endothelial cells. The inhibition of CYP1A1 and CYP1B1 protein expression caused by zinc deficiency was reversible by cellular zinc supplementation. Overall, our results strongly suggest that nutrition can modulate an environmental toxicant-induced biological outcome and that adequate levels of individual nutrients such as zinc are necessary for induction of AhR responsive genes in vascular endothelial cells.
锌具有抗炎特性，对血管内皮细胞的完整性以及心血管系统的发育和稳态至关重要。在血管内皮细胞中表达的芳基烃受体（AhR）在对外来物质暴露和心血管发育的反应中也起着重要作用。我们假设细胞内锌可以调节内皮细胞中 AhR 反应基因的诱导。为了确定锌缺乏是否会改变 AhR 配体的反应，将主动脉内皮细胞暴露于 AhR 配体 3,3'，4,4'-四氯联苯（PCB77）或β-萘黄酮（β-NF）单独或与膜可渗透锌螯合剂 TPEN 联合使用，然后测量 AhR 反应性细胞色素 P450 酶 CYP1A1 和 1B1。与载体处理的细胞相比，锌缺乏时，PCB77 诱导的 CYP1A1 活性（EROD）和 mRNA 表达均显着降低。此外，在锌缺乏的内皮细胞中，PCB77 和 β-NF 介导的 CYP1A1 和 CYP1B1 蛋白表达的上调也明显降低。锌缺乏引起的 CYP1A1 和 CYP1B1 蛋白表达的抑制作用可通过细胞内锌补充来逆转。总体而言，我们的结果强烈表明，营养可以调节环境毒物引起的生物学结果，并且个体营养素（如锌）的足够水平是诱导血管内皮细胞中 AhR 反应基因所必需的。
