ArticleAmerican journal of physiology. Lung cellular and molecular physiology2010
Rac1-mediated NADPH oxidase release of O2- regulates epithelial sodium channel activity in the alveolar epithelium.
Article in American journal of physiology. Lung cellular and molecular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- DNA oxidation after exercise: a systematic review and meta-analysis.Frontiers in physiology · 2023Pooled it
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.American journal of respiratory cell and molecular biology · 2025Article
- Endothelial ENaC as a repressor of oxidative stress and a guardian of lung capillary barrier function in bacterial and viral pneumonia.Frontiers in physiology · 2025Review
- Da-Chuan-Xiong Decoction Ameliorates Sodium Sensitivity and Plasma Norepinephrine via Attenuation of Brain Oxidative Stress in the DOCA-Salt Hypertensive Rats.International journal of hypertension · 2024Article
- Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases.Pathogens (Basel, Switzerland) · 2023Review
- NOXA1-dependent NADPH oxidase 1 signaling mediates angiotensin II activation of the epithelial sodium channel.American journal of physiology. Renal physiology · 2022Article
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm.Oxidative medicine and cellular longevity · 2020Review
- Regulation of Lung Epithelial Sodium Channels by Cytokines and Chemokines.Frontiers in immunology · 2017Review
- Hydrogen Peroxide and Sodium Transport in the Lung and Kidney.BioMed research international · 2016Review
- Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption.The Journal of biological chemistry · 2014Article
- Chronic ethanol exposure alters the lung proteome and leads to mitochondrial dysfunction in alveolar type 2 cells.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- ROS-mediated activation of Drosophila larval nociceptor neurons by UVC irradiation.BMC neuroscience · 2014Article
- Fulvene-5 inhibition of Nadph oxidases attenuates activation of epithelial sodium channels in A6 distal nephron cells.American journal of physiology. Renal physiology · 2013Article
- H2O2 regulates lung epithelial sodium channel (ENaC) via ubiquitin-like protein Nedd8.The Journal of biological chemistry · 2013Article
- Chronic alcohol ingestion changes the landscape of the alveolar epithelium.BioMed research international · 2013Review
- ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1.American journal of physiology. Cell physiology · 2013Article
- Ethanol alters alveolar fluid balance via Nadph oxidase (NOX) signaling to epithelial sodium channels (ENaC) in the lung.PloS one · 2013Article
- Curcumin nanoparticles ameliorate ICAM-1 expression in TNF-α-treated lung epithelial cells through p47 (phox) and MAPKs/AP-1 pathways.PloS one · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We examine whether alveolar cells can control release of O(2)(-) through regulated NADPH oxidase (NOX) 2 (NOX2) activity to maintain lung fluid homeostasis. Using FACS to purify alveolar epithelial cells, we show that type 1 cells robustly express each of the critical NOX components that catalyze the production of O(2)(-) (NOX2 or gp91(phox), p22(phox), p67(phox), p47(phox), and p40(phox) subunits) as well as Rac1 at substantially higher levels than type 2 cells. Immunohistochemical labeling of lung tissue shows that Rac1 expression is cytoplasmic and resides near the apical surface of type 1 cells, whereas NOX2 coimmunoprecipitates with epithelial sodium channel (ENaC). Since Rac1 is a known regulator of NOX2, and hence O(2)(-) release, we tested whether inhibition or activation of Rac1 influenced ENaC activity. Indeed, 1 microM NSC23766 inhibition of Rac1 decreased O(2)(-) output in lung cells and significantly decreased ENaC activity from 0.87 +/- 0.16 to 0.52 +/- 0.16 [mean number of channels (N) and single-channel open probability (P(o)) (NP(o)) +/- SE, n = 6; P < 0.05] in type 2 cells. NSC23766 (10 microM) decreased ENaC NP(o) from 1.16 +/- 0.27 to 0.38 +/- 0.10 (n = 6 in type 1 cells). Conversely, 10 ng/ml EGF (a known stimulator of both Rac1 and O(2)(-) release) increased ENaC NP(o) values in both type 1 and 2 cells. NP(o) values increased from 0.48 +/- 0.21 to 0.91 +/- 0.28 in type 2 cells (P < 0.05; n = 10). In type 1 cells, ENaC activity also significantly increased from 0.40 +/- 0.15 to 0.60 +/- 0.23 following EGF treatment (n = 7). Sequestering O(2)(-) using 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) compound prevented EGF activation of ENaC in both type 1 and 2 cells. In conclusion, we report that Rac1-mediated NOX2 activity is an important component in O(2)(-) regulation of ENaC.
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