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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells
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A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells

机译：锌缺乏和过量对人THP-1单核细胞中表达的基因的选择性的全局视图

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Among the micronutrients required by humans, zinc has particularly divergent modes of action. cDNA microarray and quantitative PCR technologies were used to investigate the zinc responsiveness of known genes that influence zinc homeostasis and to identify, through global screening, genes that may relate to phenotypic outcomes of altered dietary zinc intake. Human monocytic/macrophage THP-1 cells were either acutely zinc depleted, using a cell-permeable zinc-specific chelator, or were supplemented with zinc to alter intracellular zinc concentrations. Initially, genes associated with zinc homeostasis were evaluated by quantitative PCR to establish ranges for fold changes in transcript abundance that might be expected with global screening. Zinc transporter-1 and zinc transporter-7 expression increased when cellular zinc increased, whereas Zip-2 expression, the most zinc-responsive gene examined, was markedly increased by zinc depletion. Microarrays composed of approximate to22,000 elements were used to identify those genes responsive to either zinc depletion, zinc supplementation, or both conditions. Hierarchal clustering and ANCIVA revealed that approximate to5% or 1,045 genes were zinc responsive. Further sorting based on this pattern of the zinc responsiveness of these genes into seven groups revealed that 104 genes were linearly zinc responsive in a positive mode (i.e., increased expression as cellular zinc increases) and 86 genes that were linearly zinc responsive in a negative mode (i.e., decreased expression as cellular zinc increases). Expression of some genes was responsive to only zinc depletion or supplementation. Categorization by function revealed numerous genes needed for host defense were among those identified as zinc responsive, including cytokine receptors and genes associated with amplification of the Th1 immune response. [References: 42]
机译：在人类所需的微量营养素中，锌具有特别不同的作用方式。 cDNA微阵列和定量PCR技术用于研究影响锌体内稳态的已知基因的锌响应性，并通过全局筛选来鉴定与饮食中锌摄入量变化的表型结果有关的基因。使用细胞可渗透的锌特异性螯合剂使人单核细胞/巨噬细胞THP-1细胞严重缺锌，或补充锌以改变细胞内锌的浓度。最初，通过定量PCR对与锌稳态相关的基因进行评估，以建立转录物丰度倍数变化的范围，这可能是全球筛选所期望的。当细胞锌增加时，锌转运蛋白-1和锌转运蛋白7的表达增加，而锌含量最高的基因Zip-2的表达由于锌的消耗而显着增加。使用由大约22,000个元素组成的微阵列来鉴定那些对锌耗竭，锌补充或这两种情况有反应的基因。层次聚类和ANCIVA显示，大约有5％或1,045个基因对锌具有响应性。根据这些基因对锌的反应性的这种模式进一步分类为七个组，发现有104个基因在阳性模式下呈线性锌响应（即，随着细胞锌的增加而表达增加），而有86个基因在阴性模式下呈线性锌响应。 （即，表达随着细胞锌的增加而降低）。一些基因的表达仅对锌的消耗或补充有反应。按功能分类显示，宿主防御所需的许多基因属于锌反应性基因，包括细胞因子受体和与Th1免疫反应放大相关的基因。 [参考：42]

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