Zinc Transporter Genes Are Coordinately Expressed in Men and Women Independently of Dietary or Plasma Zinc

Abstract

The zinc transporter (ZnT; SLC30) and Zrt- and Irt-like protein (Zip, SLC39) zinc transporter families are integral to the maintenance of intracellular zinc concentrations. Few studies have examined the expression patterns of zinc transporter genes in human primary tissues. This study investigated the expression levels of a range of zinc transporter mRNA in the peripheral blood mononuclear cells of healthy men and women (n = 40) using quantitative real-time PCR. It also explored the relationships among zinc transporter expression levels, plasma zinc concentrations, and dietary zinc intake. The relative expression of the zinc transporter mRNA varied considerably, with ZnT7, ZnT1, and Zip1 being the most abundantly expressed. ZnT1 and Zip1 mRNA were highly correlated with one another (r = 0.9; P < 0.001) and with ZnT5, ZnT7, Zip3, and Zip10 (P < 0.001). When analyzed by gender, a correlation between the mRNA of ZnT7 and Zip3 (r = 0.6; P < 0.01) was demonstrated only in women. Zip10 mRNA was correlated with ZnT1 and Zip1 (r = 0.9; P < 0.001) in men only. In a regression analysis, plasma zinc variability was not significantly explained by dietary zinc intake, gender, age, or any individual or combination of zinc transporters. This study expands what is known about both the levels of zinc transporter gene transcription in humans and the extent of its variation in healthy men and women. The positive association between the mRNA of ZnT1 and Zip1, which have reciprocal roles in zinc transport across the plasma membrane, provides insight into the coordinated control of zinc homeostasis in humans.

Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults

“…The primary finding is a significant upregulation of MT-2A gene expression within two days of zinc supplementation, in the absence of significant change in plasma zinc concentration. Our previous report suggests coordination among components of cellular zinc homeostasis (Foster et al 2011), and the current findings extend these observations by demonstrating numerous relationships between the expression of zinc transporter and MT genes at baseline and during zinc supplementation. Specifically, the use of multiple regression models showed that the difference in MT-2A gene expression over the trial period was determined by changes in the expression of zinc transporter genes.…”

Zinc and zinc transporters in prostate carcinogenesis

“…41, 42, 43 Expression of ZnT-1 is induced by high zinc concentrations in LNCaP and PC-3 human prostate cancer cells, 44 consistent with its putative role as a zinc export protein. Indeed, one in vitro study demonstrated that induction of ZNT1 gene transcription is mediated by the binding of the metal-specific transcription factor MTF-1 to two metal response elements (MRE) in the ZnT-1 promoter.…”

“…To date, 14 mammalian ZIP members have been identified; 43 however, only ZIP1, ZIP2, ZIP3, and ZIP4 have been shown to be localized to the plasma membrane and therefore, participate in importing zinc from extracellular fluid. 41, 48–53 ZIP1 is important for the extraction of zinc from circulation as the primary source of cellular zinc, whereas ZIP2 and ZIP3 seem to be important for the retention of zinc in the cellular compartment.…”

Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

“…Plasma zinc in group A increased by 31 µg/dL, while in group B, it decreased by 25 µg/dL. As ZIP1 (importer) and ZnT1 (exporter) are among the most abundantly expressed zinc transporters [24,29] and their expressions were down-regulated and up-regulated, respectively, after short periods of zinc supplementation [6,17], we selected these markers for evaluation.…”