Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14

Ivo F. Scheiber, Neftali Ortega Alarcon, Ningning Zhao

Research output: Contribution to journalArticle

Abstract

The alveolar epithelia of the lungs require manganese (Mn) as an essential nutrient, but also provide an entry route for airborne Mn that can cause neurotoxicity. Transporters involved in Mn uptake by alveolar epithelial cells are unknown. Recently, two members of the Zrt- and Irt-like protein (ZIP) family of metal transporters, ZIP8 and ZIP14, have been identified as crucial Mn importers in vivo. ZIP8 is by far most abundantly expressed in the lungs, whereas ZIP14 expression in the lungs is low compared to other tissues. We hypothesized that Mn uptake by alveolar epithelial cells is primarily mediated by ZIP8. To test our hypothesis, we used A549 cells, a type II alveolar cell line. Mirroring the in vivo situation, A549 cells expressed higher levels of ZIP8 than cell models for the liver, intestines, and kidney. Quantification of ZIP8 and ZIP14 revealed a strong enrichment of ZIP8 over ZIP14 in A549 cells. Using siRNA technology, we identified ZIP8 and ZIP14 as the major transporters mediating Mn uptake by A549 cells. To our surprise, knockdown of either ZIP8 or ZIP14 impaired Mn accumulation to a similar extent, which we traced back to similar amounts of ZIP8 and ZIP14 at the plasma membrane. Our study highlights the importance of both ZIP8 and ZIP14 in Mn metabolism of alveolar epithelial cells.

Original languageEnglish (US)
JournalNutrients
Volume11
Issue number7
DOIs
StatePublished - Jun 28 2019

Fingerprint

Manganese
manganese
Alveolar Epithelial Cells
uptake mechanisms
cells
transporters
epithelial cells
lungs
Lung
neurotoxicity
A549 Cells
small interfering RNA
Small Interfering RNA
Intestines
intestines
plasma membrane
epithelium
Epithelium
Metals
cell lines

Keywords

  • alveolar epithelia
  • inhalation exposure
  • lung
  • manganese
  • transporter
  • ZIP14
  • ZIP8

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14. / Scheiber, Ivo F.; Alarcon, Neftali Ortega; Zhao, Ningning.

In: Nutrients, Vol. 11, No. 7, 28.06.2019.

Research output: Contribution to journalArticle

Scheiber, Ivo F. ; Alarcon, Neftali Ortega ; Zhao, Ningning. / Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14. In: Nutrients. 2019 ; Vol. 11, No. 7.
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