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Redox Biol. 2014 Jan 15;2:436-46. doi: 10.1016/j.redox.2013.12.030. eCollection 2014.

Identification of DUOX1-dependent redox signaling through protein S-glutathionylation in airway epithelial cells.

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Department of Pathology, Vermont Lung Center, College of Medicine, University of Vermont, Burlington, VT 05405, United States.
Department of Biology, College of Arts and Sciences, University of Vermont, Burlington, VT 05405, United States.
Department of Physiology, Faculty of Medicine, and "Lendulet" Peroxidase Enzyme Research Group, Semmelweis University, Budapest, Hungary.


The NADPH oxidase homolog dual oxidase 1 (DUOX1) plays an important role in innate airway epithelial responses to infection or injury, but the precise molecular mechanisms are incompletely understood and the cellular redox-sensitive targets for DUOX1-derived H2O2 have not been identified. The aim of the present study was to survey the involvement of DUOX1 in cellular redox signaling by protein S-glutathionylation, a major mode of reversible redox signaling. Using human airway epithelial H292 cells and stable transfection with DUOX1-targeted shRNA as well as primary tracheal epithelial cells from either wild-type or DUOX1-deficient mice, DUOX1 was found to be critical in ATP-stimulated transient production of H2O2 and increased protein S-glutathionylation. Using cell pre-labeling with biotin-tagged GSH and analysis of avidin-purified proteins by global proteomics, 61 S-glutathionylated proteins were identified in ATP-stimulated cells compared to 19 in untreated cells. Based on a previously established role of DUOX1 in cell migration, various redox-sensitive proteins with established roles in cytoskeletal dynamics and/or cell migration were evaluated for S-glutathionylation, indicating a critical role for DUOX1 in ATP-stimulated S-glutathionylation of β-actin, peroxiredoxin 1, the non-receptor tyrosine kinase Src, and MAPK phosphatase 1. Overall, our studies demonstrate the importance of DUOX1 in epithelial redox signaling through reversible S-glutathionylation of a range of proteins, including proteins involved in cytoskeletal regulation and MAPK signaling pathways involved in cell migration.


Cell migration; Cysteine; DUOX1; NADPH oxidase; Proteomics; S-glutathionylation

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