Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

Zhongping Deng, Lisa A. Dailey, Joleen Soukup, Jacqueline Stonehuerner, Judy D. Richards, Kimberly D. Callaghan, Funmei Yang, Andrew J. Ghio

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 Zn2+ transport interacts with iron homeostasis in these same cells. Zn2+ uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn2+ release occurred in the 4 h immediately following cell exposure to ZnSO4. 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 ZnSO4. Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn2+. Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-α, IFN-γ, 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.

Original languageEnglish (US)
Pages (from-to)803-815
Number of pages13
JournalBioMetals
Volume22
Issue number5
DOIs
StatePublished - Oct 2009

Keywords

  • Divalent metal transporter 1
  • Ferritin
  • Iron
  • Lung
  • Membrane transporters
  • Metals
  • Oxidative stress
  • Zinc compounds

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

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