Effects of long-term zinc supplementation and deprivation on gene expression in human THP-1 mononuclear cells.
Zinc is an essential trace element that is critical for cellular function and structural integrity. It has an important regulatory role in the immune system, in particular in monocytes. To identify the diverse cellular targets and mechanisms of action of zinc in this cell type, we used microarray technology to assess the effects of zinc supplementation and depletion on global gene expression. mRNA expression in the human monocytic cell line THP-1 was analyzed and compared in response to 40h supplementation with 50micromol/L zinc, or zinc deprivation by 2.5micromol/L of the membrane-permeant zinc chelator TPEN [N,N,N',N'-tetrakis-(2-pyridyl-methyl)ethylenediamine]. Analysis of microarrays consisting of approximately 19,000 unique oligonucleotides identified over 1400 genes, or approximately 7%, as zinc-sensitive. Notably, this yielded several sets of structurally or functionally related genes. Among those groups, which were mainly affected by zinc deprivation, were histones, S100 calcium and zinc binding proteins, and chemokines and their receptors. These groups of genes may mediate zinc-effects on chromatin regulation, zinc homeostasis, and chemotaxis, respectively. In addition, functional networks were analyzed, showing that the well known effect of zinc on pro-inflammatory cytokines is not limited to these genes; it acts on a number of functionally connected genes, as well. These results provide novel molecular targets and pathways that may aid in explaining the role of zinc in monocyte function.
Mazzatti
Dawn J
DJ
Unilever Corporate Research, Bedfordshire, UK.
Uciechowski
Peter
P
Hebel
Silke
S
Engelhardt
Gabriela
G
White
Andrew J
AJ
Powell
Jonathan R
JR
Rink
Lothar
L
Haase
Hajo
H
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015032:Zinc / Q000008:administration & dosage* / Q000494:pharmacology
D017931:DNA Primers; D015032:Zinc