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Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

Content Provider	Springer Nature Link
Author	Deng, Zhongping Dailey, Lisa A. Soukup, Joleen Stonehuerner, Jacqueline Richards, Judy D. Callaghan, Kimberly D. Yang, Funmei Ghio, Andrew J.
Copyright Year	2009
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.
Starting Page	803
Ending Page	815
Page Count	13
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	22
Issue Number	5
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-03-22
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Zinc compounds Iron Oxidative stress Divalent metal transporter 1 Ferritin Membrane transporters Metals Lung Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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