Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression
Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression
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DOI：
10.1093/jn/128.5.825
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发表时间：
1998-05-01
影响因子：
4.2
通讯作者：
Cousins, RJ
中科院分区：
文献类型：
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作者：
Davis, SR;McMahon, RJ;Cousins, RJ
金属硫蛋白在肠道锌吸收中的作用一直是颇有争议的话题。如果金属硫蛋白影响锌的吸收，那么诱导金属硫蛋白合成的那些因素（例如重金属、激素）应该会改变锌的吸收和体内平衡。目前的研究使用金属硫蛋白转基因小鼠（过度表达）和金属硫蛋白敲除小鼠（不表达金属硫蛋白-1或金属硫蛋白-2）来直接检查金属硫蛋白对锌吸收的影响，不依赖于金属硫蛋白诱导剂可能引起的二次效应。通过饲管给金属硫蛋白转基因和金属硫蛋白敲除小鼠施用单次口服锌剂量（0.5 mmol/kg）并测量血清锌浓度来检查锌的吸收。给药两小时后，金属硫蛋白敲除小鼠的血清锌浓度比对照品系高 2.3 倍。相反，在服用锌剂后，转基因小鼠中金属硫蛋白的浓度仅升高了对照组的三分之一。我们发现血清锌浓度与金属硫蛋白蛋白水平呈负相关。然而，金属硫蛋白敲除小鼠的肠道锌含量较高，这表明金属硫蛋白并不会通过简单地将锌隔离在粘膜中来减少锌的吸收。锌转运蛋白ZnT-1的表达与血清锌水平直接相关，且与金属硫蛋白水平无关。这些结果进一步支持金属硫蛋白是在锌摄入量增加时降低锌吸收效率的重要成分。
A role for metallothionein in intestinal zinc absorption has been the subject of considerable debate. If metallothionein affects zinc absorption, then those factors that induce metallothionein synthesis (e.g., heavy metals, hormones) should alter zinc absorption and homeostasis. The present studies used metallothionein transgenic mice (overexpressing) and metallothionein knockout mice (no expression of metallothionein-1 or metallothionein-2) to examine directly the effects of metallothionein on zinc absorption, independent of secondary effects that could be caused by metallothionein inducers. Zinc absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by feeding tube to metallothionein transgenic and metallothionein knockout mice and measuring the serum zinc concentration. Two hours after the dose, the serum zinc concentration was 2.3 times higher in metallothionein knockout mice than in their control strain. Conversely, the concentration was elevated only one third as much in the metallothionein transgenic mice as in their controls after the zinc dose. We found that the serum zinc concentration was inversely related to the level of metallothionein protein. The intestinal zinc content was higher in the metallothionein knockout mice, however, suggesting that metallothionein did not reduce zinc absorption by simply sequestering zinc in the mucosa. The expression of the zinc transporter ZnT-1 was directly related to the serum zinc level and was independent of the level of metallothionein. These results further support metallothionein as an important component for reducing the efficiency of zinc absorption at elevated zinc intakes.