Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

Abstract

Despite recurrent exposure to zinc through inhalation of ambient air pollution particles, relatively little information is known about the homeostasis of this metal in respiratory epithelial cells. We describe zinc uptake and release by respiratory epithelial cells and test the postulate that Zn(2+) transport interacts with iron homeostasis in these same cells. Zn(2+) uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn(2+) release occurred in the 4 h immediately following cell exposure to ZnSO(4). Regarding metal importers, mRNA for Zip1 and Zip2 showed no change after respiratory epithelial cell exposure to zinc while mRNA for divalent metal transporter (DMT)1 increased. Western blot assay for DMT1 protein supported an elevated expression of this transport protein following zinc exposure. RT-PCR confirmed mRNA for the metal exporters ZnT1 and ZnT4 with the former increasing after ZnSO(4). Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn(2+). Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-alpha, IFN-gamma, and endotoxin, was associated with significantly decreased intracellular zinc transport. Finally, incubations of respiratory epithelial cells with both zinc sulfate and ferric ammonium citrate resulted in elevated intracellular concentrations of both metals. We conclude that exposure to zinc increases iron uptake by respiratory epithelial cells. Elevations in cell iron can possibly affect an increased expression of DMT1 and ferritin which function to diminish oxidative stress. Comparable to other metal exposures, changes in iron homeostasis may contribute to the biological effects of zinc in specific cells and tissues.

Low Doses of Cadmium Chloride and Methallothionein-1-Bound Cadmium Display Different Accumulation Kinetics and Induce Different Genes in Cells of the Human Nephron

“…Although DMT-1 primarily is an Fe-transporting molecule, a recent study identified DMT-1 as a Zn-transporting molecule as well [25]. Therefore, the dramatic inhibition of cellular Cd accumulation in the presence of Zn may also be indicative for a role of DMT-1 in cellular Cd transport.…”

Associations between Ionomic Profile and Metabolic Abnormalities in Human Population

“…However, most of the previous studies have focused on the role(s) of single or a few ions simultaneously. Given delicate homeostatic controlled nature, relationships of multi-ions are extremely complicated with synergistic or antagonistic interactions under various physical and pathologic conditions [13], [14]. Owing to methodological limitation which could only estimate a few ions at one time, it remains unclear whether a single ion alone or a network of several ions affects metabolic outcomes in a different manner.…”

“…However, the interaction among multiple ions might result in much more complex relationships within ion modules/networks than simply linear dependences [13], [14]. To overcome this problem, we applied mutual information in our analysis.…”

The critical role of intracellular zinc in adenosine A2 receptor activation induced cardioprotection against reperfusion injury

“…A multi-element standard (Spex Certiprep, Metuchen, NJ) was used to calibrate the instrument. The limits of detection approximated 1 ppb [15]. Zinc levels were expressed as % changes in zinc concentration s during reperfusion relative to the values measured immediately before the onset of reperfusion (0′).…”