ArticleThe Journal of biological chemistry2013
H2O2 regulates lung epithelial sodium channel (ENaC) via ubiquitin-like protein Nedd8.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway.Redox biology · 2025Article
- Identification of phytochemical compounds ofHeliyon · 2023Article
- Enhanced epithelial sodium channel activity in neonatal Scnn1b mouse lung attenuates high oxygen-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Dual Role of Hydrogen Peroxide as an Oxidant in Pneumococcal Pneumonia.Antioxidants & redox signaling · 2021Review
- Epilepsy channelopathies go neddy: stabilizing NaV1.1 channels by neddylation.The Journal of clinical investigation · 2021Article
- The necessity of NEDD8/Rub1 for vitality and its association with mitochondria-derived oxidative stress.Redox biology · 2020Review
- Epithelial sodium channels in endothelial cells mediate diet-induced endothelium stiffness and impaired vascular relaxation in obese female mice.Metabolism: clinical and experimental · 2019Article
- Proteasome lid bridges mitochondrial stress with Cdc53/Cullin1 NEDDylation status.Redox biology · 2019Article
- Oxidative stress, autophagy and airway ion transport.American journal of physiology. Cell physiology · 2019Review
- RAGE-induced changes in the proteome of alveolar epithelial cells.Journal of proteomics · 2018Article
- Conserved cysteines in the finger domain of the epithelial NaThe Journal of biological chemistry · 2018Article
- Knockout of mitochondrial voltage-dependent anion channel type 3 increases reactive oxygen species (ROS) levels and alters renal sodium transport.The Journal of biological chemistry · 2018Article
- Hydrogen Peroxide and Sodium Transport in the Lung and Kidney.BioMed research international · 2016Review
- Inhibitory role of reactive oxygen species in the differentiation of multipotent vascular stem cells into vascular smooth muscle cells in rats: a novel aspect of traditional culture of rat aortic smooth muscle cells.Cell and tissue research · 2015Article
- Oxidized glutathione (GSSG) inhibits epithelial sodium channel activity in primary alveolar epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension.American journal of physiology. Renal physiology · 2015Review
- Receptor for advanced glycation end-products regulates lung fluid balance via protein kinase C-gp91(phox) signaling to epithelial sodium channels.American journal of respiratory cell and molecular biology · 2015Article
- Hydrogen peroxide stimulation of CFTR reveals an Epac-mediated, soluble AC-dependent cAMP amplification pathway common to GPCR signalling.British journal of pharmacology · 2015Article
- Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption.The Journal of biological chemistry · 2014Article
- Oxygen in the regulation of intestinal epithelial transport.The Journal of physiology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Redundancies in both the ubiquitin and epithelial sodium transport pathways allude to their importance of proteolytic degradation and ion transport in maintaining normal cell function. The classical pathway implicated in ubiquitination of the epithelial sodium channel (ENaC) involves Nedd4-2 regulation of sodium channel subunit expression and has been studied extensively studied. However, less attention has been given to the role of the ubiquitin-like protein Nedd8. Here we show that Nedd8 plays an important role in the ubiquitination of ENaC in alveolar epithelial cells. We report that the Nedd8 pathway is redox-sensitive and that under oxidizing conditions Nedd8 conjugation to Cullin-1 is attenuated, resulting in greater surface expression of α-ENaC. This observation was confirmed in our electrophysiology studies in which we inhibited Nedd8-activating enzyme using MLN4924 (a specific Nedd8-activating enzyme inhibitor) and observed a marked increase in ENaC activity (measured as the product of the number of channels (N) and the open probability (Po) of a channel). These results suggest that ubiquitination of lung ENaC is redox-sensitive and may have significant implications for our understanding of the role of ENaC in pulmonary conditions where oxidative stress occurs, such as pulmonary edema and acute lung injury.
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