Antioxidant-like properties of zinc in activated endothelial cells
Antioxidant-like properties of zinc in activated endothelial cells
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DOI：
10.1080/07315724.1999.10718843
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发表时间：
1999-04-01
影响因子：
3.5
通讯作者：
McClain, CJ
中科院分区：
文献类型：
--
作者：
Hennig, B;Meerarani, P;McClain, CJ
目的：本研究的目的是检验以下假设：内皮细胞缺锌可能会增强某些脂质和细胞因子介导的炎症反应，可能是通过与细胞氧化应激增加相关的机制。我们的实验方法是比较细胞缺锌和补锌的条件与氧化应激介导的血管内皮细胞分子和生化变化。方法：为了研究我们的假设，猪肺动脉来源的内皮细胞在含有 1% 胎牛血清的培养基中培养八天，从而耗尽了锌。随后，将内皮细胞暴露于富含或不含锌（10μM）的培养基中两天，然后暴露于肿瘤坏死因子-α（TNF，500U/mL）或亚油酸（90μM），然后测量氧化应激（DCF荧光）、核因子κB（NF-κB）或激活蛋白1（AP-1）的激活以及炎症细胞因子白细胞介素6的产生(IL-6)。 结果：用脂肪酸或 TNF 处理后，缺锌内皮细胞的氧化应激显着增加。之前补充锌可以部分阻止氧化应激的增加。缺锌和脂肪酸处理可上调氧化应激敏感转录因子 NF-kappa B。补充锌可显着降低脂肪酸介导的上调。 AP-1 也获得了类似的结果。此外。在用脂肪酸或TNF处理后，缺锌内皮细胞中IL-6的内皮细胞产生增加。补充锌可以部分阻止炎症细胞因子产生的增加。讨论：我们之前的数据清楚地表明，锌是维持内皮完整性的保护性且关键的营养素。目前的数据表明，锌可能部分通过抑制内皮细胞功能障碍中的氧化应激反应事件来抗动脉粥样硬化。这可能对理解动脉粥样硬化的机制有影响。
Objective: The objective of this study was to test the hypothesis that zinc deficiency in endothelial cells may potentiate the inflammatory response mediated by certain lipids and cytokines, possibly via mechanisms associated with increased cellular oxidative stress. Our experimental approach was to compare conditions of cellular zinc deficiency and zinc supplementation with oxidative stress-mediated molecular and biochemical changes in vascular endothelial cells.Methods: To investigate our hypothesis, porcine pulmonary artery-derived endothelial cells were depleted of zinc by culture in media containing 1% fetal bovine serum for eight days. Subsequently, endothelial cells were exposed to media enriched with or without zinc (10 mu M) for two days, followed by exposure to tither tumor necrosis factor-alpha (TNF, 500 U/mL) or linoleic acid (90 mu M) before measurement of oxidative stress (DCF fluorescence), activation of nuclear factor kappa B (NF-kappa B) or activator protein-1 (AP-1) and production of the inflammatory cytokine interleukin 6 (IL-6).Results: Oxidative stress was increased markedly in zinc-deficient endothelial cells following treatment with fatty acid or TNF. This increase in oxidative stress was partially blocked by prior zinc supplementation. The oxidative stress-sensitive transcription factor NF-kappa B was up-regulated by zinc deficiency and fatty acid treatment. The up-regulation mediated by fatty acids was markedly reduced by zinc supplementation. Similar results were obtained with AP-1. Furthermore. endothelial cell production of IL-6 was increased in zinc-deficient endothelial cells following treatment with fatty acids or TNF. This increase in production of inflammatory cytokines was partially blocked by zinc supplementation.Discussion: Our previous data clearly show that zinc is a protective and critical nutrient for maintenance of endothelial integrity. The present data suggest that zinc may in part be antiatherogenic by inhibiting oxidative stress-responsive events in endothelial cell dysfunction. This may have implications in understanding mechanisms of atherosclerosis.