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蛋白质组学分析显示,锌限制的人体红细胞中波形蛋白的表达上调。

Proteomic analysis shows the upregulation of erythrocyte dematin in zinc-restricted human subjects.

机构信息

Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL, USA.

出版信息

Am J Clin Nutr. 2012 May;95(5):1096-102. doi: 10.3945/ajcn.111.032862. Epub 2012 Mar 28.

DOI:10.3945/ajcn.111.032862
PMID:22456662
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3325834/
Abstract

BACKGROUND

Although the importance of adequate zinc intake has been known for decades, the estimated global prevalence of zinc deficiency remains high. This substantiates the need for a specific and sensitive status assessment tool.

OBJECTIVE

The objective was to evaluate erythrocyte zinc transporters as candidate molecules with the potential of being a biomarker of dietary zinc status in humans.

DESIGN

A 24-d observational study with acclimation (7 d, 10.4 mg Zn/d), zinc-depletion (10 d, 0.3 mg Zn/d), and zinc-repletion (7 d, 29.5 mg Zn/d) phases was conducted in healthy men (n = 9). Proteomic approaches including Western blot analyses and tandem mass spectrometry were implemented to identify the zinc responsiveness of selected red blood cell membrane proteins.

RESULTS

Zinc transporter 1 (ZnT1) and Zrt/Irt-like proteins ZIP8 and ZIP10 were detected in human erythrocyte membranes. No effects of short-term dietary zinc depletion were observed on the amounts of these proteins. However, changes in a cytoskeletal protein, dematin, by zinc depletion were identified through the nonspecific signals produced by an anti-ZIP8 antibody. This response was further validated by a dematin-specific antibody and with erythrocytes collected from mice fed a zinc-deficient diet.

CONCLUSIONS

The presence of ZnT1, ZIP8, and ZIP10 in human red blood cells implicates their role in the regulation of cellular zinc metabolism in the human erythroid system. The zinc responsiveness of membrane dematin suggests its capability to serve as a biomarker for dietary zinc depletion and its involvement in impaired erythroid membrane fragility by zinc restriction. This trial was registered at clinicaltrials.gov as NCT01221129.

摘要

背景

尽管几十年来人们已经认识到摄入足够锌的重要性,但全球锌缺乏的估计患病率仍然很高。这证实了需要一种特定和敏感的状态评估工具。

目的

本研究旨在评估红细胞锌转运体作为候选分子,其有可能成为人类膳食锌状况的生物标志物。

设计

在健康男性(n=9)中进行了一项为期 24 天的观察性研究,包括适应期(7 天,10.4 mg Zn/d)、锌耗竭期(10 天,0.3 mg Zn/d)和锌补充期(7 天,29.5 mg Zn/d)。采用蛋白质组学方法,包括 Western blot 分析和串联质谱法,来鉴定选定红细胞膜蛋白的锌反应性。

结果

锌转运蛋白 1(ZnT1)和 Zrt/Irt 样蛋白 ZIP8 和 ZIP10 存在于人红细胞膜中。短期饮食锌耗竭对这些蛋白的含量没有影响。然而,通过锌耗竭产生的非特异性信号检测到细胞骨架蛋白 dematin 的变化。通过针对 dematin 的特异性抗体和用缺锌饮食喂养的小鼠的红细胞进一步验证了这一反应。

结论

ZnT1、ZIP8 和 ZIP10 存在于人红细胞中,提示其在人类红细胞系统中调节细胞内锌代谢的作用。膜蛋白 dematin 的锌反应性表明其有潜力作为膳食锌耗竭的生物标志物,并表明其在锌限制下参与受损的红细胞膜脆性。这项试验在 clinicaltrials.gov 上注册为 NCT01221129。

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