ArticleThe Journal of biological chemistry2015
High CO2 levels cause skeletal muscle atrophy via AMP-activated kinase (AMPK), FoxO3a protein, and muscle-specific Ring finger protein 1 (MuRF1).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Biomarkers of Skeletal Muscle Atrophy Based on Atrogenes Evaluation: A Systematic Review and Meta-Analysis Study.International journal of molecular sciences · 2025Pooled it
- Carbon dioxide levels in neonates: what are safe parameters?Pediatric research · 2022Pooled it
- Hypercapnia enhances airway smooth muscle contractility via STIM1-dependent Ca2+ signaling.JCI insight · 2026Article
- Carbon dioxide is a triple vasodilator.Cardiovascular research · 2026Article
- Plant‑derived natural products alleviate dexamethasone‑induced skeletal muscle atrophy by modulating FoxO (Review).International journal of molecular medicine · 2026Review
- Impact of hypoxic air quality on resistance training effect in different normobaric hypoxia environments.European journal of applied physiology · 2026Article
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Long-term DNA methylation changes induced by age and elevated COSkeletal muscle · 2025Article
- PRMT1 (protein arginine methyltransferase 1) is essential for neuromuscular junction and mitochondrial homeostasis via mitophagy regulation.Autophagy · 2025Article
- SIRT2 attenuates stress-induced skeletal muscle atrophy by inhibiting glucocorticoid receptor signalling.bioRxiv : the preprint server for biology · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- USP33 promotes pulmonary microvascular endothelial cell pyroptosis by stabilizing TRAF2 through deubiquitination.Histology and histopathology · 2025Article
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Hypercapnia outcome in COVID-19 acute respiratory distress syndrome patients on mechanical ventilator: A retrospective observational cohort.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2025Article
- Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.International journal of molecular sciences · 2024Review
- 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
- Mild and moderate chronic hypercapnia elicit distinct transcriptomic responses of immune function in cardiorespiratory nuclei.Physiological genomics · 2023Article
- Hypercapnia alters mitochondrial gene expression and acylcarnitine production in monocytes.Immunology and cell biology · 2023Article
- High Prevalence of Non-Responders Based on Quadriceps Force after Pulmonary Rehabilitation in COPD.Journal of clinical medicine · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
Abstract
Patients with chronic obstructive pulmonary disease, acute lung injury, and critical care illness may develop hypercapnia. Many of these patients often have muscle dysfunction which increases morbidity and impairs their quality of life. Here, we investigated whether hypercapnia leads to skeletal muscle atrophy. Mice exposed to high CO2 had decreased skeletal muscle wet weight, fiber diameter, and strength. Cultured myotubes exposed to high CO2 had reduced fiber diameter, protein/DNA ratios, and anabolic capacity. High CO2 induced the expression of MuRF1 in vivo and in vitro, whereas MuRF1(-/-) mice exposed to high CO2 did not develop muscle atrophy. AMP-activated kinase (AMPK), a metabolic sensor, was activated in myotubes exposed to high CO2, and loss-of-function studies showed that the AMPKα2 isoform is necessary for muscle-specific ring finger protein 1 (MuRF1) up-regulation and myofiber size reduction. High CO2 induced AMPKα2 activation, triggering the phosphorylation and nuclear translocation of FoxO3a, and leading to an increase in MuRF1 expression and myotube atrophy. Accordingly, we provide evidence that high CO2 activates skeletal muscle atrophy via AMPKα2-FoxO3a-MuRF1, which is of biological and potentially clinical significance in patients with lung diseases and hypercapnia.
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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.