ArticleFree radical biology & medicine2018
Crosstalk between autophagy and oxidative stress regulates proteolysis in the diaphragm during mechanical ventilation.
Article in Free radical biology & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Comparative effectiveness of inspiratory muscle training approaches within intensive care unit-acquired weakness prevention and rehabilitation strategies: a systematic review and component network meta-analysis.BMC pulmonary medicine · 2026Pooled it
- Outcomes in critically ill patients after diaphragmatic stimulation on ventilator-induced diaphragmatic dysfunction: a systematic review.European journal of physical and rehabilitation medicine · 2023Pooled it
- Muscle satellite cell dysfunction in critical illness: niche biology, regenerative failure, and implications for recovery.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial ROS dyshomeostasis: a key driver of accelerated supraspinatus atrophy after rotator cuff injury.Frontiers in physiology · 2026Review
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Dietary nitrate preserves mitochondrial bioenergetics and mitochondrial protein synthesis rates during short-term immobilization in mice.The Journal of physiology · 2025Article
- Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025Review
- Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.International journal of molecular sciences · 2024Article
- Dimorphic effect of TFE3 in determining mitochondrial and lysosomal content in muscle following denervation.Skeletal muscle · 2024Article
- Research progress on the pathogenesis and treatment of ventilator-induced diaphragm dysfunction.Heliyon · 2023Review
- Aberrant mitochondrial dynamics contributes to diaphragmatic weakness induced by mechanical ventilation.PNAS nexus · 2023Article
- Autophagy ablation in skeletal muscles worsens sepsis-induced muscle wasting, impairs whole-body metabolism, and decreases survival.iScience · 2023Article
- Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting.Journal of cachexia, sarcopenia and muscle · 2023Article
- Autophagy in Cancer Progression and Therapeutics.International journal of molecular sciences · 2023Article
- Advances in mitochondria-centered mechanism behind the roles of androgens and androgen receptor in the regulation of glucose and lipid metabolism.Frontiers in endocrinology · 2023Review
- Intensive Care Unit Acquired Weakness Is Associated with Rapid Changes to Skeletal Muscle Proteostasis.Cells · 2022Article
- Effects of Hyperbaric Oxygen Preconditioning on Doxorubicin Cardiorespiratory Toxicity.Antioxidants (Basel, Switzerland) · 2022Article
- Identification of the co-differentially expressed hub genes involved in the endogenous protective mechanism against ventilator-induced diaphragm dysfunction.Skeletal muscle · 2022Article
- Redox signaling regulates skeletal muscle remodeling in response to exercise and prolonged inactivity.Redox biology · 2022Review
- Article
Corrections and comments
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Authors and funding
10 authors at 10 institutions in 2 countries.
Funding
Abstract
Mechanical ventilation (MV) results in the rapid development of ventilator-induced diaphragm dysfunction (VIDD). While the mechanisms responsible for VIDD are not fully understood, recent data reveal that prolonged MV activates autophagy in the diaphragm, which may occur as a result of increased cellular reactive oxygen species (ROS) production. Therefore, we tested the hypothesis that (1) accelerated autophagy is a key contributor to VIDD; and that (2) oxidative stress is required to increase the expression of autophagy genes in the diaphragm. Our findings reveal that targeted inhibition of autophagy in the rat diaphragm prevented MV-induced muscle atrophy and contractile dysfunction. Attenuation of VIDD in these animals occurred as a result of increased diaphragm concentration of the antioxidant catalase and reduced mitochondrial ROS emission, which corresponded to reductions in the activity of calpain and caspase-3. To determine if increased ROS production is required for the upregulation of autophagy biomarkers in the diaphragm, rats that were administered the mitochondrial-targeted peptide SS-31 during MV. Results from this study demonstrated that mitochondrial ROS production in the diaphragm during MV is required for the increased expression of key autophagy genes (i.e. LC3, Atg7, Atg12, Beclin1 and p62), as well as for increased activity of cathepsin L. Together, these data reveal that autophagy is required for VIDD, and that autophagy inhibition reduces MV-induced diaphragm ROS production and prevents a positive feedback loop whereby increased autophagy is stimulated by oxidative stress, resulting in further increases in ROS and autophagy.
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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.