ArticleMolecular and cellular biology2011
Hypoxia leads to Na,K-ATPase downregulation via Ca(2+) release-activated Ca(2+) channels and AMPK activation.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 160 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
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
- Epithelial NaJournal of sleep research · 2026Article
- Iron overload suppresses LKB1 and induces IL36G anti-tumor immunity in PDAC metastasis.Science advances · 2026Article
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Loss of AMPK potentiates inflammation by activating the infammasome in a preclinical mouse model of TBI.NeuroImmune pharmacology and therapeutics · 2026Article
- Magnesium Deficiency Accelerates Gut Aging and Increases Susceptibility to Colitis.Aging cell · 2026Article
- The role of Na,K‑ATPase in lung diseases (Review).Molecular medicine reports · 2025Review
- Assessment of the safety of hypoxia-primed mesenchymal stem cells derived from umbilical cord and adipose tissues in animals.Scientific reports · 2025Article
- AMPK function in uterine vasculature and placenta at high altitude.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The Bidirectional Role of Hypoxia-Inducible Factor 1 Alpha in Vascular Dementia Caused by Chronic Cerebral Hypoperfusion.Molecular neurobiology · 2025Review
- The shifting landscape of the preterm brain.Neuron · 2025Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.The Journal of membrane biology · 2024Review
- Metabolic programs drive function of therapeutic NK cells in hypoxic tumor environments.Science advances · 2024Article
- Cancer Metabolism under Limiting Oxygen Conditions.Cold Spring Harbor perspectives in medicine · 2024Review
- The NLRP3 inflammasome in ischemic stroke.Frontiers in stroke · 2024Review
- Adipose-Derived Mesenchymal Stem Cells Protect Endothelial Cells from Hypoxic Injury by Suppressing Terminal UPR In Vivo and In Vitro.International journal of molecular sciences · 2023Article
- A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress.The EMBO journal · 2023Article
- Atovaquone exerts its anticancer effect by inhibiting NaVeterinary world · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
To maintain cellular ATP levels, hypoxia leads to Na,K-ATPase inhibition in a process dependent on reactive oxygen species (ROS) and the activation of AMP-activated kinase α1 (AMPK-α1). We report here that during hypoxia AMPK activation does not require the liver kinase B1 (LKB1) but requires the release of Ca(2+) from the endoplasmic reticulum (ER) and redistribution of STIM1 to ER-plasma membrane junctions, leading to calcium entry via Ca(2+) release-activated Ca(2+) (CRAC) channels. This increase in intracellular Ca(2+) induces Ca(2+)/calmodulin-dependent kinase kinase β (CaMKKβ)-mediated AMPK activation and Na,K-ATPase downregulation. Also, in cells unable to generate mitochondrial ROS, hypoxia failed to increase intracellular Ca(2+) concentration while a STIM1 mutant rescued the AMPK activation, suggesting that ROS act upstream of Ca(2+) signaling. Furthermore, inhibition of CRAC channel function in rat lungs prevented the impairment of alveolar fluid reabsorption caused by hypoxia. These data suggest that during hypoxia, calcium entry via CRAC channels leads to AMPK activation, Na,K-ATPase downregulation, and alveolar epithelial dysfunction.
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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.