Regulation of hyperoxia-induced neonatal lung injury via post-translational cysteine redox modifications.

Autor: Zhang T; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA., Day NJ; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA., Gaffrey M; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA., Weitz KK; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA., Attah K; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA., Mimche PN; Division of Microbiology and Immunology, Department of Pathology, University of Utah Molecular Medicine Program, Salt Lake City, UT, USA., Paine R 3rd; Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA., Qian WJ; Integrative Omics Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA. Electronic address: Weijun.Qian@pnnl.gov., Helms MN; Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. Electronic address: my.helms@hsc.utah.edu.
Jazyk: angličtina
Zdroj: Redox biology [Redox Biol] 2022 Sep; Vol. 55, pp. 102405. Date of Electronic Publication: 2022 Jul 19.
DOI: 10.1016/j.redox.2022.102405
Abstrakt: Preterm infants and patients with lung disease often have excess fluid in the lungs and are frequently treated with oxygen, however long-term exposure to hyperoxia results in irreversible lung injury. Although the adverse effects of hyperoxia are mediated by reactive oxygen species, the full extent of the impact of hyperoxia on redox-dependent regulation in the lung is unclear. In this study, neonatal mice overexpressing the beta-subunit of the epithelial sodium channel (β-ENaC) encoded by Scnn1b and their wild type (WT; C57Bl6) littermates were utilized to study the pathogenesis of high fraction inspired oxygen (FiO 2 )-induced lung injury. Results showed that O 2 -induced lung injury in transgenic Scnn1b mice is attenuated following chronic O 2 exposure. To test the hypothesis that reversible cysteine-redox-modifications of proteins play an important role in O 2 -induced lung injury, we performed proteome-wide profiling of protein S-glutathionylation (SSG) in both WT and Scnn1b overexpressing mice maintained at 21% O 2 (normoxia) or FiO 2 85% (hyperoxia) from birth to 11-15 days postnatal. Over 7700 unique Cys sites with SSG modifications were identified and quantified, covering more than 3000 proteins in the lung. In both mouse models, hyperoxia resulted in a significant alteration of the SSG levels of Cys sites belonging to a diverse range of proteins. In addition, substantial SSG changes were observed in the Scnn1b overexpressing mice exposed to hyperoxia, suggesting that ENaC plays a critically important role in cellular regulation. Hyperoxia-induced SSG changes were further supported by the results observed for thiol total oxidation, the overall level of reversible oxidation on protein cysteine residues. Differential analyses reveal that Scnn1b overexpression may protect against hyperoxia-induced lung injury via modulation of specific processes such as cell adhesion, blood coagulation, and proteolysis. This study provides a landscape view of protein oxidation in the lung and highlights the importance of redox regulation in O 2 -induced lung injury.
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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