Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation
Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation
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DOI：
10.1152/ajpregu.00439.2015
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发表时间：
2016-03-01
影响因子：
2.8
通讯作者：
Komai, Michio
中科院分区：
文献类型：
--
作者：
Hashimoto, Ayako;Nakagawa, Miki;Komai, Michio
全身性和细胞性锌稳态由ZIP和ZNT锌转运蛋白精密控制。因此，对它们的表达特性进行详细的表征是非常重要的。在这些转运蛋白中，ZIP4是控制全身锌稳态的主要转运蛋白，因为它在小肠中具有不可或缺的锌吸收功能。在这项研究中，我们使用我们制备的抗ZIP4的单抗，仔细研究了ZIP4蛋白在大鼠小肠中对锌状态的反应，并将其与膜结合的碱性磷酸酶(ALP)的锌反应活性进行了对比。我们发现，ZIP4的积累对缺锌的反应比之前认为的更快。缺锌饮食后1天，空肠积累量增加。在小肠中，ZIP4蛋白在空肠中的表达高于十二指肠，并伴随着ALP活性的降低，提示空肠更容易发生缺锌。此外，通过监测ZIP4在十二指肠和空肠中的积累水平和ALP活性，我们重申，哺乳期缺锌可能会以性别差异的方式瞬时改变后代的血糖水平，而不会影响锌代谢的动态平衡控制。这证实了哺乳期的锌营养对后代的健康极其重要。这些结果表明，ZIP4的快速积累为理解全身性锌稳态调控的分子基础提供了重大的概念性进展，ZIP4蛋白的积累特性有助于密切评估锌的状况。
Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely.