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Superoxide-dependent iron uptake: a new role for anion exchange protein 2.

Publication ,  Journal Article
Ghio, AJ; Nozik-Grayck, E; Turi, J; Jaspers, I; Mercatante, DR; Kole, R; Piantadosi, CA
Published in: Am J Respir Cell Mol Biol
December 2003

Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by incompletely understood mechanisms. We tested the hypothesis that human bronchial epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide-dependent ferri-reductase activity involving anion exchange protein 2 (AE2) and extracellular bicarbonate (HCO3-). HBE cells that constitutively express AE2 mRNA by reverse transcriptase-polymerase chain reaction and AE2 protein by Western analysis avidly transported NTBI after exposure to either Fe2+ or Fe3+, but reduction of Fe3+ to Fe2+ was first required. The ability of HBE cells to reduce Fe3+ and transport Fe2+ was inhibited by active extracellular superoxide dismutase (SOD). Similarly, HBE cells that overexpress Cu,Zn SOD after adenoviral infection with AdSOD1 showed diminished iron uptake. The role of AE2 in iron uptake was indicated by three lines of evidence: (i) lack of both iron reduction and iron transport in bicarbonate-free buffer at controlled pH, (ii) failure of HBE cells treated with stilbene AE inhibitors to reduce Fe3+ or transport iron, and (iii) inhibition of iron uptake in HBE cells by inhibition of AE2 protein expression with antisense oligonucleotides. We thus disclose a novel ferri-reductase mechanism of NTBI uptake by human lung cells that employs superoxide exchange for HCO3- by AE2 protein in the plasma membrane.

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Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

December 2003

Volume

29

Issue

6

Start / End Page

653 / 660

Location

United States

Related Subject Headings

  • Superoxides
  • Superoxide Dismutase-1
  • Superoxide Dismutase
  • SLC4A Proteins
  • Respiratory System
  • Respiratory Mucosa
  • Oxidation-Reduction
  • Oligonucleotides, Antisense
  • Membrane Proteins
  • Iron
 

Citation

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Ghio, A. J., Nozik-Grayck, E., Turi, J., Jaspers, I., Mercatante, D. R., Kole, R., & Piantadosi, C. A. (2003). Superoxide-dependent iron uptake: a new role for anion exchange protein 2. Am J Respir Cell Mol Biol, 29(6), 653–660. https://doi.org/10.1165/rcmb.2003-0070OC
Ghio, Andrew J., Eva Nozik-Grayck, Jennifer Turi, Ilona Jaspers, Danielle R. Mercatante, Ryszard Kole, and Claude A. Piantadosi. “Superoxide-dependent iron uptake: a new role for anion exchange protein 2.Am J Respir Cell Mol Biol 29, no. 6 (December 2003): 653–60. https://doi.org/10.1165/rcmb.2003-0070OC.
Ghio AJ, Nozik-Grayck E, Turi J, Jaspers I, Mercatante DR, Kole R, et al. Superoxide-dependent iron uptake: a new role for anion exchange protein 2. Am J Respir Cell Mol Biol. 2003 Dec;29(6):653–60.
Ghio, Andrew J., et al. “Superoxide-dependent iron uptake: a new role for anion exchange protein 2.Am J Respir Cell Mol Biol, vol. 29, no. 6, Dec. 2003, pp. 653–60. Pubmed, doi:10.1165/rcmb.2003-0070OC.
Ghio AJ, Nozik-Grayck E, Turi J, Jaspers I, Mercatante DR, Kole R, Piantadosi CA. Superoxide-dependent iron uptake: a new role for anion exchange protein 2. Am J Respir Cell Mol Biol. 2003 Dec;29(6):653–660.

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

December 2003

Volume

29

Issue

6

Start / End Page

653 / 660

Location

United States

Related Subject Headings

  • Superoxides
  • Superoxide Dismutase-1
  • Superoxide Dismutase
  • SLC4A Proteins
  • Respiratory System
  • Respiratory Mucosa
  • Oxidation-Reduction
  • Oligonucleotides, Antisense
  • Membrane Proteins
  • Iron