ArticleJournal of applied physiology (Bethesda, Md. : 1985)2011
Lung injury caused by high tidal volume mechanical ventilation and hyperoxia is dependent on oxidant-mediated c-Jun NH2-terminal kinase activation.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Bench evidence, bedside uncertainty: hyperoxia, mechanical ventilation and lung injury.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Role of the two-pore domain potassium channel TREK-1 in hyperoxia- and mechanical stretch-induced alveolar epithelial injury.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy.Frontiers in cell and developmental biology · 2026Review
- Activation of TREK-1 (American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Article
- Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- MC-PPEA as a new and more potent inhibitor of CLP-induced sepsis and pulmonary inflammation than FK866.Drug design, development and therapy · 2017Article
- Oxygenation, inflammatory response and lung injury during one lung ventilation in rabbits using inspired oxygen fraction of 0.6 vs. 1.0.Journal of biomedical research · 2016Article
- The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia-induced lung injury.Critical care medicine · 2014Article
- Pleiotropic effects of interleukin-6 in a "two-hit" murine model of acute respiratory distress syndrome.Pulmonary circulation · 2014Article
- Article
- Regulation of interleukin-6 secretion by the two-pore-domain potassium channel Trek-1 in alveolar epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Hyperoxic acute lung injury.Respiratory care · 2013Review
- Regulation of Monocyte Chemotactic Protein-1 secretion by the Two-Pore-Domain Potassium (K2P) channel TREK-1 in human alveolar epithelial cells.American journal of translational research · 2013Article
- Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in mice.American journal of respiratory cell and molecular biology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Both prolonged exposure to hyperoxia and large tidal volume mechanical ventilation can each independently cause lung injury. However, the combined impact of these insults is poorly understood. We recently reported that preexposure to hyperoxia for 12 h, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone (Makena et al. Am J Physiol Lung Cell Mol Physiol 299: L711-L719, 2010). The upstream mechanisms of this lung injury and apoptosis have not been clearly elucidated. We hypothesized that lung injury in this model was dependent on oxidative signaling via the c-Jun NH(2)-terminal kinases (JNK). We, therefore, evaluated lung injury and apoptosis in the presence of N-acetyl-cysteine (NAC) in both mouse and cell culture models, and we provide evidence that NAC significantly inhibited lung injury and apoptosis by reducing the production of ROS, activation of JNK, and apoptosis. To confirm JNK involvement in apoptosis, cells treated with a specific JNK inhibitor, SP600125, and subjected to preexposure to hyperoxia, followed by mechanical stretch, exhibited significantly reduced evidence of apoptosis. In conclusion, lung injury and apoptosis caused by preexposure to hyperoxia, followed by high tidal volume mechanical ventilation, induces ROS-mediated activation of JNK and mitochondrial-mediated apoptosis. NAC protects lung injury and apoptosis by inhibiting ROS-mediated activation of JNK and downstream proapoptotic signaling.
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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.