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Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

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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.

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Abbreviations

DMSO:

Dimethylsulfoxide

DMT1:

Divalent metal transporter 1

DNPH:

2,4-Dinitrophenylhydrazine

DPBS:

Dulbecco’s phosphate buffered saline

HBE:

Human bronchial epithelial

ICPOES:

Inductively coupled plasma optical emission spectroscopy

KGM:

Keratinocyte growth medium

LDH:

Lactate dehydrogenase

MTT:

Methylthiazoletetrazolium

PM:

Particulate matter

TCA:

Trichloroacetic acid

Tf:

Transferrin

TfR:

Transferrin receptor

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Authors and Affiliations

  1. Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC, 27599-7310, USA

    Zhongping Deng

  2. National Shanghai Center for Drug Safety Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China

    Zhongping Deng

  3. National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, Durham, NC, 27711, USA

    Lisa A. Dailey, Joleen Soukup, Jacqueline Stonehuerner, Judy D. Richards & Andrew J. Ghio

  4. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, 78284, USA

    Kimberly D. Callaghan & Funmei Yang

  5. Human Studies Division, US EPA, 104 Mason Farm Road, Campus Box 7315, Chapel Hill, NC, 27599-7315, USA

    Andrew J. Ghio

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  1. Zhongping Deng
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  2. Lisa A. Dailey
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  3. Joleen Soukup
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  4. Jacqueline Stonehuerner
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  7. Funmei Yang
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  8. Andrew J. Ghio
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Correspondence to Andrew J. Ghio.

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Deng, Z., Dailey, L.A., Soukup, J. et al. Zinc transport by respiratory epithelial cells and interaction with iron homeostasis. Biometals 22, 803–815 (2009). https://doi.org/10.1007/s10534-009-9227-2

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