Hennig B, Wang Y, Ramasamy S, McClain C J
Department of Nutrition and Food Science, University of Kentucky, Lexington.
J Nutr. 1993 Jun;123(6):1003-9. doi: 10.1093/jn/123.6.1003.
Some nutrients influence the metabolic response of cytokines such as tumor necrosis factor. Inadequate levels of the essential trace element zinc may play a role in tumor necrosis factor-induced disruption of the vascular endothelial barrier function. To test this hypothesis, endothelial cells cultured on polycarbonate filters or culture plates were exposed to six different treatments for 3 d: medium 199 enriched with 5% fetal bovine serum (control), control+two levels of supplemental zinc (7.7 and 12.3 mumol/L medium), tumor necrosis factor (5 x 10(5) U/L) and tumor necrosis factor+the two levels of Zn as noted previously. Endothelial barrier function, expressed as albumin transfer across cultured endothelial monolayers, was not affected by Zn enrichment alone. Tumor necrosis factor treatment significantly increased albumin transfer compared with control cultures. The lower concentration of Zn partially and the higher concentration totally prevented the tumor necrosis factor-induced increase in albumin transfer. The increase in cytosolic release of [3H]adenine (marker of cell injury) induced by tumor necrosis factor was prevented by added Zn. Tumor necrosis factor treatment significantly decreased angiotensin-converting enzyme activity, and tumor necrosis factor also decreased activities of two other membrane-bound enzymes, total ATPase and Ca(2+)-ATPase. These activities all were restored by Zn enrichment. Tumor necrosis factor treatment caused a decrease in cellular Zn concentration, which was prevented when the culture media were enriched with Zn. These data suggest that an important relationship exists between Zn status and tumor necrosis factor-induced endothelial cell dysfunction.
一些营养素会影响细胞因子如肿瘤坏死因子的代谢反应。必需微量元素锌水平不足可能在肿瘤坏死因子诱导的血管内皮屏障功能破坏中起作用。为了验证这一假设，将培养在聚碳酸酯滤膜或培养板上的内皮细胞进行6种不同处理，持续3天：含5%胎牛血清的199培养基（对照）、对照 + 两种补充锌的水平（培养基中7.7和12.3 μmol/L）、肿瘤坏死因子（5×10⁵ U/L）以及肿瘤坏死因子 + 上述两种锌水平。以内皮单层培养物中白蛋白转运来表示的内皮屏障功能，单独的锌富集并未对其产生影响。与对照培养物相比，肿瘤坏死因子处理显著增加了白蛋白转运。较低浓度的锌部分阻止且较高浓度的锌完全阻止了肿瘤坏死因子诱导的白蛋白转运增加。添加锌可阻止肿瘤坏死因子诱导的[³H]腺嘌呤胞质释放增加（细胞损伤标志物）。肿瘤坏死因子处理显著降低了血管紧张素转换酶活性，并且肿瘤坏死因子还降低了另外两种膜结合酶——总ATP酶和Ca²⁺ - ATP酶的活性。这些活性通过锌富集得以恢复。肿瘤坏死因子处理导致细胞锌浓度降低，当培养基中添加锌时这种降低被阻止。这些数据表明锌状态与肿瘤坏死因子诱导的内皮细胞功能障碍之间存在重要关系。
