Cysteine-rich intestinal protein and intestinal metallothionein: an inverse relationship as a conceptual model for zinc absorption in rats.
Cysteine-rich intestinal protein and intestinal metallothionein: an inverse relationship as a conceptual model for zinc absorption in rats.
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DOI：
10.1093/jn/122.1.89
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
J. Hempe;R. Cousins
中科院分区：
文献类型：
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作者：
J. Hempe;R. Cousins
膳食锌可能部分通过抑制肠道金属硫蛋白来调节锌的吸收，但其机制尚不清楚。我们最近发现富含半胱氨酸的肠蛋白（CRIP）在锌的跨粘膜转运过程中与锌结合，CRIP可能作为细胞内锌的载体发挥作用。本实验研究CRIP和金属硫蛋白与锌的相互作用，以评估其在锌吸收机制中的潜在作用。肠金属硫蛋白的浓度较低，锌的吸收率较高，从孤立的肠循环喂低锌饮食的大鼠相比，那些喂高锌饮食或肠外锌诱导金属硫蛋白的合成。锌的状态并不影响表观CRIP浓度，但显着改变了65锌在肠胞液中的分布，凝胶过滤HPLC测定。与高锌状态的大鼠相比，在低锌饮食的大鼠中，更多的65 Zn与CRIP相关（40 vs. 14%），更少的65 Zn与金属硫蛋白结合（4 vs. 52 - 59%）。胞腔锌浓度也影响~（65）Zn在胞液中的分布。随着管腔锌浓度从5 μ mol/L增加到300 μ mol/L，CRIP结合从管腔吸收的65Zn逐渐减少（从42%到25%）。总的来说，这些数据表明，CRIP是一种饱和的，细胞内锌转运蛋白，金属硫蛋白抑制锌的吸收结合锌与CRIP竞争。一个假设的模型，跨细胞锌吸收的机制，涉及金属硫蛋白和CRIP的介绍和讨论。
Dietary zinc may regulate zinc absorption in part via the inhibitory effect of intestinal metallothionein, but the mechanism is unknown. We recently showed that cysteine-rich intestinal protein (CRIP) binds zinc during transmucosal zinc transport, and that CRIP may function as an intracellular zinc carrier. The present experiments examine the interaction of CRIP and metallothionein with zinc to evaluate their potential roles in the mechanism of zinc absorption. Intestinal metallothionein concentrations were lower and zinc absorption rates from isolated intestinal loops were higher in rats fed a low zinc diet compared with those fed a high zinc diet or given parenteral zinc to induce metallothionein synthesis. Zinc status did not affect the apparent CRIP concentration, but markedly altered the distribution of 65Zn in intestinal cytosol as determined by gel filtration HPLC. More 65Zn was associated with CRIP (40 vs. 14%) and less was bound to metallothionein (4 vs. 52-59%) in rats fed the low zinc diet compared with rats of high zinc status. Luminal zinc concentration also affected the distribution of 65Zn in the cytosol. CRIP bound progressively less (from 42 to 25%) of the 65Zn taken up from the lumen as the luminal zinc concentration was increased from 5 to 300 mumol/L. Collectively these data suggest that CRIP is a saturable, intracellular zinc transport protein, and that metallothionein inhibits zinc absorption by binding zinc in competition with CRIP. A hypothetical model for the mechanism of transcellular zinc absorption involving metallothionein and CRIP is presented and discussed.