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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

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)...

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Autores principales: Murgia, Chiara, Grosser, Dion, Truong-Tran, Ai Q., Roscioli, Eugene, Michalczyk, Agnes, Ackland, Margaret Leigh, Stoltenberg, Meredin, Danscher, Gorm, Lang, Carol, Knight, Darryl, Perozzi, Giuditta, Ruffin, Richard E., Zalewski, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257720/
https://www.ncbi.nlm.nih.gov/pubmed/22254085
http://dx.doi.org/10.3390/nu3110910
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author Murgia, Chiara
Grosser, Dion
Truong-Tran, Ai Q.
Roscioli, Eugene
Michalczyk, Agnes
Ackland, Margaret Leigh
Stoltenberg, Meredin
Danscher, Gorm
Lang, Carol
Knight, Darryl
Perozzi, Giuditta
Ruffin, Richard E.
Zalewski, Peter
author_facet Murgia, Chiara
Grosser, Dion
Truong-Tran, Ai Q.
Roscioli, Eugene
Michalczyk, Agnes
Ackland, Margaret Leigh
Stoltenberg, Meredin
Danscher, Gorm
Lang, Carol
Knight, Darryl
Perozzi, Giuditta
Ruffin, Richard E.
Zalewski, Peter
author_sort Murgia, Chiara
collection PubMed
description 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.
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spelling pubmed-32577202012-01-17 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 Leigh Stoltenberg, Meredin Danscher, Gorm Lang, Carol Knight, Darryl Perozzi, Giuditta Ruffin, Richard E. Zalewski, Peter Nutrients Article 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. MDPI 2011-10-25 /pmc/articles/PMC3257720/ /pubmed/22254085 http://dx.doi.org/10.3390/nu3110910 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Murgia, Chiara
Grosser, Dion
Truong-Tran, Ai Q.
Roscioli, Eugene
Michalczyk, Agnes
Ackland, Margaret Leigh
Stoltenberg, Meredin
Danscher, Gorm
Lang, Carol
Knight, Darryl
Perozzi, Giuditta
Ruffin, Richard E.
Zalewski, Peter
Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title_full Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title_fullStr Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title_full_unstemmed Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title_short Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation
title_sort apical localization of zinc transporter znt4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257720/
https://www.ncbi.nlm.nih.gov/pubmed/22254085
http://dx.doi.org/10.3390/nu3110910
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