ArticleBritish journal of pharmacology2012
AMP-activated protein kinase (AMPK)-dependent and -independent pathways regulate hypoxic inhibition of transepithelial Na+ transport across human airway epithelial cells.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- AMPK function in uterine vasculature and placenta at high altitude.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species.Cells · 2025Article
- Submersion and hypoxia inhibit alveolar epithelial NaRespiratory research · 2023Article
- Prospective Application of Ferroptosis in Hypoxic Cells for Tumor Radiotherapy.Antioxidants (Basel, Switzerland) · 2022Review
- FSH mediates estradiol synthesis in hypoxic granulosa cells by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 signaling pathway.The Journal of biological chemistry · 2022Article
- AMPK-mTOR Signaling and Cellular Adaptations in Hypoxia.International journal of molecular sciences · 2021Review
- Protective impact ofToxicology research · 2021Article
- The role of AMPK in regulation of NaJournal of muscle research and cell motility · 2021Review
- E-cigarette constituents propylene glycol and vegetable glycerin decrease glucose uptake and its metabolism in airway epithelial cells in vitro.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- AMPK and the Need to Breathe and Feed: What's the Matter with Oxygen?International journal of molecular sciences · 2020Review
- Activation of AMPK under Hypoxia: Many Roads Leading to Rome.International journal of molecular sciences · 2020Review
- The Fast Lane of Hypoxic Adaptation: Glucose Transport Is Modulated via A HIF-Hydroxylase-AMPK-Axis in Jejunum Epithelium.International journal of molecular sciences · 2019Article
- Hydrogen sulfide decreases β-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Perinatal oxygen in the developing lung.Canadian journal of physiology and pharmacology · 2015Review
- Regulation of ion channels and transporters by AMP-activated kinase (AMPK).Channels (Austin, Tex.) · 2014Review
- Does epithelial sodium channel hyperactivity contribute to cystic fibrosis lung disease?The Journal of physiology · 2013Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposePulmonary transepithelial Na(+) transport is reduced by hypoxia, but in the airway the regulatory mechanisms remain unclear. We investigated the role of AMPK and ROS in the hypoxic regulation of apical amiloride-sensitive Na(+) channels and basolateral Na(+) K(+) ATPase activity. EXPERIMENTAL APPROACH: H441 human airway epithelial cells were used to examine the effects of hypoxia on Na(+) transport, AMP : ATP ratio and AMPK activity. Lentiviral constructs were used to modify cellular AMPK abundance and activity; pharmacological agents were used to modify cellular ROS. KEY
resultsAMPK was activated by exposure to 3% or 0.2% O(2) for 60 min in cells grown in submerged culture or when fluid (0.1 mL·cm(-2) ) was added to the apical surface of cells grown at the air-liquid interface. Only 0.2% O(2) activated AMPK in cells grown at the air-liquid interface. AMPK activation was associated with elevation of cellular AMP:ATP ratio and activity of the upstream kinase LKB1. Hypoxia inhibited basolateral ouabain-sensitive I(sc) (I(ouabain) ) and apical amiloride-sensitive Na(+) conductance (G(Na+) ). Modification of AMPK activity prevented the effect of hypoxia on I(ouabain) (Na(+) K(+) ATPase) but not apical G(Na+) . Scavenging of superoxide and inhibition of NADPH oxidase prevented the effect of hypoxia on apical G(Na+) (epithelial Na(+) channels). CONCLUSIONS AND IMPLICATIONS: Hypoxia activates AMPK-dependent and -independent pathways in airway epithelial cells. Importantly, these pathways differentially regulate apical Na(+) channels and basolateral Na(+) K(+) ATPase activity to decrease transepithelial Na(+) transport. Luminal fluid potentiated the effect of hypoxia and activated AMPK, which could have important consequences in lung disease conditions.
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