ArticleAmerican journal of respiratory cell and molecular biology2013
Protein kinase A-Iα regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO(2) concentrations.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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
29 citing papers in PubMed, 41 citations in OpenAlex.
- Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study.Journal of translational medicine · 2019Trial
- Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial.Metabolites · 2026Article
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Alveolar-capillary endocytosis and trafficking in acute lung injury and acute respiratory distress syndrome.Frontiers in immunology · 2024Review
- A retrospective study of the role of hypercapnia in patients with acromegaly.BMC pulmonary medicine · 2023Article
- Hypercapnia in COPD: Causes, Consequences, and Therapy.Journal of clinical medicine · 2022Review
- Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease.The Journal of membrane biology · 2021Article
- Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Elevated COInterface focus · 2021Review
- TRAF2 Is a Novel Ubiquitin E3 Ligase for the Na,K-ATPase β-Subunit That Drives Alveolar Epithelial Dysfunction in Hypercapnia.Frontiers in cell and developmental biology · 2021Article
- Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction.Frontiers in physiology · 2021Review
- Hypercapnia: An Aggravating Factor in Asthma.Journal of clinical medicine · 2020Review
- Hypercapnia Regulates Gene Expression and Tissue Function.Frontiers in physiology · 2020Review
- The role of hypercapnia in acute respiratory failure.Intensive care medicine experimental · 2019Review
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- DR region of NaScientific reports · 2018Article
- Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments.Journal of cardiovascular development and disease · 2018Review
- Effects of hypercapnia on the lung.The Journal of physiology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Elevated concentrations of CO2 (hypercapnia) lead to alveolar epithelial dysfunction by promoting Na,K-ATPase endocytosis. In the present report, we investigated whether the CO2/HCO3(-) activated soluble adenylyl cyclase (sAC) regulates this process. We found that hypercapnia increased the production of cyclic adenosine monophosphate (cAMP) and stimulated protein kinase A (PKA) activity via sAC, which was necessary for Na,K-ATPase endocytosis. During hypercapnia, cAMP was mainly produced in specific microdomains in the proximity of the plasma membrane, leading to PKA Type Iα activation. In alveolar epithelial cells exposed to high CO2 concentrations, PKA Type Iα regulated the time-dependent phosphorylation of the actin cytoskeleton component α-adducin at serine 726. Cells expressing small hairpin RNA for PKAc, dominant-negative PKA Type Iα, small interfering RNA for α-adducin, and α-adducin with serine 726 mutated to alanine prevented Na,K-ATPase endocytosis. In conclusion, we provide evidence for a new mechanism by which hypercapnia via sAC, cAMP, PKA Type Iα, and α-adducin regulates Na,K-ATPase endocytosis in alveolar epithelial cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.