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Am J Physiol Lung Cell Mol Physiol 283: L791-L798, 2002. First published June 5, 2002; doi:10.1152/ajplung.00398.2001
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Vol. 283, Issue 4, L791-L798, October 2002

Oxidative stress activates anion exchange protein 2 and AP-1 in airway epithelial cells

Jennifer L. Turi1, Ilona Jaspers2, Lisa A. Dailey3, Michael C. Madden3, Luisa E. Brighton2, Jacqueline D. Carter3, Eva Nozik-Grayck1, Claude A. Piantadosi4, and Andrew J. Ghio3

1 Department of Pediatrics, Duke University Medical Center; 4 Department of Internal Medicine, Duke University Medical Center, Durham 27710; 2 Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599; and 3 National Health and Environmental Effects Research Laboratory, Office of Research and Development, Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Anion exchange protein 2 (AE2) is a membrane-bound protein that mediates chloride-bicarbonate exchange. In addition to regulating intracellular pH and cell volume, AE2 exports superoxide (O<UP><SUB>2</SUB><SUP>−</SUP></UP>·) to the extracellular matrix in an HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>-dependent process. Given this ability to export O<UP><SUB>2</SUB><SUP>−</SUP></UP>·, we hypothesized that expression of AE2 in the lung is regulated by oxidative stress. AE2 mRNA and protein expression was measured by RT-PCR and Western blot analysis, respectively, in differentiated human bronchial epithelial cells exposed to H2O2 (100 µM). Alterations in in vivo AE2 protein expression were evaluated in lung tissue of rats exposed to 70% O2. The role of transcription factor activator protein (AP)-1 in oxidant regulation of AE2 was evaluated by EMSA and by immunoblotting of nuclear phospho-c-jun. Results show increased AE2 mRNA and protein expression after oxidant exposure. This was preceded by transient increases in DNA binding of AE2-specific AP-1 and phosphorylation of c-jun. This study demonstrates that AE2 expression is regulated by oxidative stress in airway epithelial cells and that this regulation correlates with activation of AP-1.

superoxide; ion transport; gene regulation; activator protein-1


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