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Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation

Murgia, Chiara, Grosser, Dion, Truong-Tran, Ai Q., Roscioli, Eugene, Michalczyk, Agnes, Ackland, Margaret L., Stoltenberg, Meredin, Danscher, Gorm, Lang, Carol, Knight, Darryl, Perozzi, Giuditta, Ruffin, Richard E. and Zalewski, Peter 2011, Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation, Nutrients, vol. 3, no. 11, pp. 910-928.

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Title Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation
Author(s) Murgia, Chiara
Grosser, Dion
Truong-Tran, Ai Q.
Roscioli, Eugene
Michalczyk, Agnes
Ackland, Margaret L.
Stoltenberg, Meredin
Danscher, Gorm
Lang, Carol
Knight, Darryl
Perozzi, Giuditta
Ruffin, Richard E.
Zalewski, Peter
Journal name Nutrients
Volume number 3
Issue number 11
Start page 910
End page 928
Total pages 19
Publisher M D P I
Place of publication Basel, Switzerland
Publication date 2011
ISSN 2072-6643
Keyword(s) airway epithelium
airway inflammation
asthma
Se-Autometallography (Se-AMG)
zinc
zinc transporter
zinquin
ZnT4
Summary The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.
Language eng
Field of Research 110704 Cellular Immunology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2011, M D P I
Persistent URL http://hdl.handle.net/10536/DRO/DU:30044201

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.