ArticleThe Journal of clinical investigation2003
Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-zeta.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 310 citations in OpenAlex.
- Glycohypoxia: a hypothesis linking chronic hyperglycemia to functional hypoxia and diabetic complications in type 2 diabetes.Medical gas research · 2026Review
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026Article
- LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer.International journal of biological sciences · 2026Article
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- Protective effects of Tanshinone IIA preconditioning against hypobaric hypoxia-induced lung injury in a rat model.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Enhancement of Hypoxia Tolerance of Gibel Carp (Antioxidants (Basel, Switzerland) · 2025Article
- Membrane ATPases and Mitochondrial Proteins in Fetal Cerebellum After Exposure to L-Glutamate During Gestation.Membranes · 2025Article
- Mechanisms of impaired alveolar fluid clearance.Anatomical record (Hoboken, N.J. : 2007) · 2025Review
- Hypoxia Modulates Transmembrane Prostatic Acid Phosphatase (TM-PAP) in MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Na,K-ATPase mediated and cardiotonic induced signaling in health and disease.Frontiers in physiology · 2025Review
- Astilbin exerts a neuroprotective effect by upregulating the signaling of nuclear NF-E2-related factor 2Heliyon · 2024Article
- Outcomes and relevance of emergency percutaneous coronary angiography and intervention after resuscitated cardiac arrest: a retrospective study.BMC cardiovascular disorders · 2024Article
- Identified and potential internalization signals involved in trafficking and regulation of NaMolecular and cellular biochemistry · 2024Review
- Article
- The effect of cytochrome c on Na,K-ATPase.Journal of bioenergetics and biomembranes · 2024Article
- Article
- Na,K-ATPase activity promotes macropinocytosis in colon cancer via Wnt signaling.Biology open · 2024Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
During ascent to high altitude and pulmonary edema, the alveolar epithelial cells (AEC) are exposed to hypoxic conditions. Hypoxia inhibits alveolar fluid reabsorption and decreases Na,K-ATPase activity in AEC. We report here that exposure of AEC to hypoxia induced a time-dependent decrease of Na,K-ATPase activity and a parallel decrease in the number of Na,K-ATPase alpha(1) subunits at the basolateral membrane (BLM), without changing its total cell protein abundance. These effects were reversible upon reoxygenation and specific, because the plasma membrane protein GLUT1 did not decrease in response to hypoxia. Hypoxia caused an increase in mitochondrial reactive oxygen species (ROS) levels that was inhibited by antioxidants. Antioxidants prevented the hypoxia-mediated decrease in Na,K-ATPase activity and protein abundance at the BLM. Hypoxia-treated AEC deficient in mitochondrial DNA (rho(0) cells) did not have increased levels of ROS, nor was the Na,K-ATPase activity inhibited. Na,K-ATPase alpha(1) subunit was phosphorylated by PKC in hypoxia-treated AEC. In AEC treated with a PKC-zeta antagonist peptide or with the Na,K-ATPase alpha(1) subunit lacking the PKC phosphorylation site (Ser-18), hypoxia failed to decrease Na,K-ATPase abundance and function. Accordingly, we provide evidence that hypoxia decreases Na,K-ATPase activity in AEC by triggering its endocytosis through mitochondrial ROS and PKC-zeta-mediated phosphorylation of the Na,K-ATPase alpha(1) subunit.
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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.