A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells

Robert J. Cousins, Raymond K. Blanchard, Michael P. Popp, Li Liu, Jay Cao, J. Bernadette Moore, Calvert L. Green

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

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 ≈22,000 elements were used to identify those genes responsive to either zinc depletion, zinc supplementation, or both conditions. Hierarchal clustering and ANOVA revealed that ≈5% 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.

Original languageEnglish (US)
Pages (from-to)6952-6957
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number12
DOIs
StatePublished - Jun 10 2003
Externally publishedYes

Keywords

  • Functional genomics
  • Genomics
  • Immunology
  • Microarray
  • Nutrition

ASJC Scopus subject areas

  • General

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