McMahon R J, Cousins R J
Food Science and Human Nutrition Department and Center for Nutritional Sciences, University of Florida, Gainesville, FL 32611, USA.
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4841-6. doi: 10.1073/pnas.95.9.4841.
The understanding of mechanisms controlling zinc absorption and metabolism at the molecular level has advanced recently. Kinetics of zinc transport have been investigated for many years, but only recently have genes coding for proteins thought to be involved in the transport process been cloned. Four putative zinc transporters, known as ZnT-1 through ZnT-4, have now been described. Among these transporters, only ZnT-1 is ubiquitously expressed. In this report, we examine the pattern of ZnT-1 expression in the intestine and analyze the regulation of ZnT-1 by dietary zinc in both the intestine and liver. Immunofluorescence demonstrated that intestinal ZnT-1 was most abundant at the basolateral surface of enterocytes lining the villi of the duodenum and jejunum. By Western blot analysis, intestinal and liver ZnT-1 protein migrated as a 42- and 36-kDa protein, respectively. Dietary zinc supplementation elevated the level of intestinal ZnT-1 mRNA and protein approximately 50% and 10%, respectively, but had no effect in the liver. In response to an acute oral zinc dose, the level of intestinal ZnT-1 mRNA was up-regulated 8-fold, without a corresponding increase in ZnT-1 protein. Conversely, the acute oral dose did not affect liver ZnT-1 mRNA, but resulted in a 5-fold increase in liver ZnT-1 protein. These results represent studies on the expression of intestinal and hepatic ZnT-1 in an intact animal model. The data suggest that ZnT-1 is at least part of the mechanism by which dietary zinc is absorbed and that, despite the zinc responsiveness of the ZnT-1 gene, additional factors may be regulating the steady-state level of ZnT-1 transporter protein.
近年来，在分子水平上对控制锌吸收和代谢机制的理解有了进展。锌转运的动力学已经研究多年，但直到最近，编码被认为参与转运过程的蛋白质的基因才被克隆出来。现已描述了四种假定的锌转运体，即锌转运体1至4（ZnT-1至ZnT-4）。在这些转运体中，只有ZnT-1在全身广泛表达。在本报告中，我们研究了ZnT-1在肠道中的表达模式，并分析了饮食锌对肠道和肝脏中ZnT-1的调节作用。免疫荧光显示，肠道ZnT-1在十二指肠和空肠绒毛肠上皮细胞的基底外侧表面最为丰富。通过蛋白质印迹分析，肠道和肝脏中的ZnT-1蛋白分别以42 kDa和36 kDa的蛋白形式迁移。饮食中补充锌分别使肠道ZnT-1 mRNA和蛋白水平升高约50%和10%，但对肝脏没有影响。对急性口服锌剂量的反应中，肠道ZnT-1 mRNA水平上调了8倍，而ZnT-1蛋白没有相应增加。相反，急性口服剂量不影响肝脏ZnT-1 mRNA，但导致肝脏ZnT-1蛋白增加了5倍。这些结果代表了在完整动物模型中对肠道和肝脏ZnT-1表达的研究。数据表明，ZnT-1至少是饮食锌吸收机制的一部分，并且尽管ZnT-1基因对锌有反应，但可能还有其他因素在调节ZnT-1转运蛋白的稳态水平。
