ArticleThe Journal of biological chemistry2012
Hypercapnia induces cleavage and nuclear localization of RelB protein, giving insight into CO2 sensing and signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial.Metabolites · 2026Article
- 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
- Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.International journal of molecular sciences · 2024Article
- Addition of 5% COAmerican journal of respiratory and critical care medicine · 2021Article
- Ubiquitin is a carbon dioxide-binding protein.Science advances · 2021Article
- Elevated COInterface focus · 2021Review
- Carbon dioxide-dependent signal transduction in mammalian systems.Interface focus · 2021Review
- Carbon dioxide as a drug in neonatology.Pediatric research · 2021Article
- Hypercapnia: An Aggravating Factor in Asthma.Journal of clinical medicine · 2020Review
- High COAmerican journal of respiratory cell and molecular biology · 2020Article
- Hypercapnia Regulates Gene Expression and Tissue Function.Frontiers in physiology · 2020Review
- The role of hypercapnia in acute respiratory failure.Intensive care medicine experimental · 2019Review
- Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated miR-133a-RhoA signaling.Science translational medicine · 2018Article
- Carbon dioxide-dependent regulation of NF-κB family members RelB and p100 gives molecular insight into COThe Journal of biological chemistry · 2017Article
- Effects of hypercapnia on the lung.The Journal of physiology · 2017Review
- Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter.International journal of molecular sciences · 2017Review
- Hypercapnia Suppresses the HIF-dependent Adaptive Response to Hypoxia.The Journal of biological chemistry · 2016Article
- Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression.Journal of biomolecular screening · 2016Article
- Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator-dependent anion and fluid secretion in airway epithelia.The Journal of physiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbon dioxide (CO(2)) is increasingly being appreciated as an intracellular signaling molecule that affects inflammatory and immune responses. Elevated arterial CO(2) (hypercapnia) is encountered in a range of clinical conditions, including chronic obstructive pulmonary disease, and as a consequence of therapeutic ventilation in acute respiratory distress syndrome. In patients suffering from this syndrome, therapeutic hypoventilation strategy designed to reduce mechanical damage to the lungs is accompanied by systemic hypercapnia and associated acidosis, which are associated with improved patient outcome. However, the molecular mechanisms underlying the beneficial effects of hypercapnia and the relative contribution of elevated CO(2) or associated acidosis to this response remain poorly understood. Recently, a role for the non-canonical NF-κB pathway has been postulated to be important in signaling the cellular transcriptional response to CO(2). In this study, we demonstrate that in cells exposed to elevated CO(2), the NF-κB family member RelB was cleaved to a lower molecular weight form and translocated to the nucleus in both mouse embryonic fibroblasts and human pulmonary epithelial cells (A549). Furthermore, elevated nuclear RelB was observed in vivo and correlated with hypercapnia-induced protection against LPS-induced lung injury. Hypercapnia-induced RelB processing was sensitive to proteasomal inhibition by MG-132 but was independent of the activity of glycogen synthase kinase 3β or MALT-1, both of which have been previously shown to mediate RelB processing. Taken together, these data demonstrate that RelB is a CO(2)-sensitive NF-κB family member that may contribute to the beneficial effects of hypercapnia in inflammatory diseases of the lung.
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Registered trials
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