ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
ENaC activity and expression is decreased in the lungs of protein kinase C-α knockout mice.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
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- Ureaplasma-driven inhibition of the epithelial Na+ transport in fetal alveolar cells: A novel mechanism of Ureaplasma-mediated preterm lung disease.PLoS pathogens · 2025Article
- Positive Regulation of Cellular Proteins by Influenza Virus for Productive Infection.International journal of molecular sciences · 2025Review
- Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Submersion and hypoxia inhibit alveolar epithelial NaRespiratory research · 2023Article
- Regulation of Epithelial Sodium Transport by SARS-CoV-2 Is Closely Related with Fibrinolytic System-Associated Proteins.Biomolecules · 2023Review
- Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment-From Mice to Men.Biomedicines · 2022Review
- Vitamin E acetate as linactant in the pathophysiology of EVALI.Medical hypotheses · 2020Article
- Upregulation of the WNK4 Signaling Pathway Inhibits Epithelial Sodium Channels of Mouse Tracheal Epithelial Cells After Influenza A Infection.Frontiers in pharmacology · 2019Article
- Pre-B-cell colony enhancing factor regulates the alveolar epithelial sodium-water transport system through the ERK and AKT pathways.American journal of translational research · 2019Article
- α-Ketoglutarate stimulates pendrin-dependent ClAmerican journal of physiology. Renal physiology · 2018Article
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Novel mechanisms for crotonaldehyde-induced lung edema.Oncotarget · 2017Article
- Alveolar nonselective channels are ASIC1a/α-ENaC channels and contribute to AFC.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation.Scientific reports · 2017Article
- Hypercapnia Impairs ENaC Cell Surface Stability by Promoting Phosphorylation, Polyubiquitination and Endocytosis of β-ENaC in a Human Alveolar Epithelial Cell Line.Frontiers in immunology · 2017Article
- Cytokine-Ion Channel Interactions in Pulmonary Inflammation.Frontiers in immunology · 2017Review
- Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells.International journal of biological sciences · 2016Review
- Role of epithelial sodium channels in the regulation of lung fluid homeostasis.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Inhibition of ENaC by endothelin-1.Vitamins and hormones · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We used a PKC-α knockout model to investigate the regulation of alveolar epithelial Na(+) channels (ENaC) by PKC. Primary alveolar type II (ATII) cells were subjected to cell-attached patch clamp. In the absence of PKC-α, the open probability (Po) of ENaC was decreased by half compared with wild-type mice. The channel density (N) was also reduced in the knockout mice. Using in vivo biotinylation, membrane localization of all three ENaC subunits (α, β, and γ) was decreased in the PKC-α knockout lung, compared with the wild-type. Confocal microscopy of lung slices showed elevated levels of reactive oxygen species (ROS) in the lungs of the PKC-α knockout mice vs. the wild-type. High levels of ROS in the knockout lung can be explained by a decrease in both cytosolic and mitochondrial superoxide dismutase activity. Elevated levels of ROS in the knockout lung activates PKC-δ and leads to reduced dephosphorylation of ERK1/2 by MAP kinase phosphatase, which in turn causes increased internalization of ENaC via ubiquitination by the ubiquitin-ligase Nedd4-2. In addition, in the knockout lung, PKC-δ activates ERK, causing a decrease in ENaC density at the apical alveolar membrane. PKC-δ also phosphorylates MARCKS, leading to a decrease in ENaC Po. The effects of ROS and PKC-δ were confirmed with patch-clamp experiments on isolated ATII cells in which the ROS scavenger, Tempol, or a PKC-δ-specific inhibitor added to patches reversed the observed decrease in ENaC apical channel density and Po. These results explain the decrease in ENaC activity in PKC-α knockout lung.
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