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

Hristova, Milena and Veith, Carmen and Habibovic, Aida and Lam, Ying-Wai and Deng, Bin and Geiszt, Miklós (2014) Identification of DUOX1-dependent redox signaling through protein S-glutathionylation in airway epithelial cells. REDOX BIOLOGY, 2 (1). pp. 436-446. ISSN 2213-2317, ESSN: 2213-2317


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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. © 2014 The Authors.

Item Type: Article
Uncontrolled Keywords: S-glutathionylation; proteomics; NADPH OXIDASE; DUOX1; CYSTEINE; cell migration
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 04 Nov 2014 15:16
Last Modified: 04 Nov 2014 15:16

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