ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study.Journal of translational medicine · 2016Trial
- Loss of Myonuclei and Transcriptional Activity During Diaphragm Atrophy in Critically Ill Patients.Journal of cachexia, sarcopenia and muscle · 2026Article
- 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
- Irisin attenuates ventilator-induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK.Journal of cellular and molecular medicine · 2024Article
- From bedside to recovery: exercise therapy for prevention of post-intensive care syndrome.Journal of intensive care · 2024Review
- Identification of the co-differentially expressed hub genes involved in the endogenous protective mechanism against ventilator-induced diaphragm dysfunction.Skeletal muscle · 2022Article
- Prolonged Mechanical Ventilation: Outcomes and Management.Journal of clinical medicine · 2022Review
- Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study.International journal of molecular sciences · 2021Article
- Acute liver injury following acetaminophen administration does not activate atrophic pathways in the mouse diaphragm.Scientific reports · 2021Article
- Characterization of Signalling Pathways That Link Apoptosis and Autophagy to Cell Death Induced by Estrone Analogues Which Reversibly Depolymerize Microtubules.Molecules (Basel, Switzerland) · 2021Article
- Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?Critical care research and practice · 2020Review
- Ethyl pyruvate attenuates ventilation-induced diaphragm dysfunction through high-mobility group box-1 in a murine endotoxaemia model.Journal of cellular and molecular medicine · 2019Article
- Effects of exercise preconditioning and HSP72 on diaphragm muscle function during mechanical ventilation.Journal of cachexia, sarcopenia and muscle · 2019Article
- Ventilator-induced diaphragm dysfunction: translational mechanisms lead to therapeutical alternatives in the critically ill.Intensive care medicine experimental · 2019Review
- Endurance exercise protects skeletal muscle against both doxorubicin-induced and inactivity-induced muscle wasting.Pflugers Archiv : European journal of physiology · 2019Review
- Interactions between Cytosolic Phospholipase A2 Activation and Mitochondrial Reactive Oxygen Species Production in the Development of Ventilator-Induced Diaphragm Dysfunction.Oxidative medicine and cellular longevity · 2019Article
- Ventilator-induced diaphragm dysfunction in critical illness.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Attenuation of ventilation-induced diaphragm dysfunction through toll-like receptor 4 and nuclear factor-κB in a murine endotoxemia model.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Nutritional and metabolic stressors on ovine oocyte development and granulosa cell functions in vitro.Cell stress & chaperones · 2018Article
- Diaphragmatic dysfunction in sepsis due to severe acute pancreatitis complicated by intra-abdominal hypertension.The Journal of international medical research · 2018Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Mechanical ventilation (MV) is a life-saving measure in many critically ill patients. However, prolonged MV results in diaphragm dysfunction that contributes to the frequent difficulty in weaning patients from the ventilator. The molecular mechanisms underlying ventilator-induced diaphragm dysfunction (VIDD) remain poorly understood. We report here that MV induces myonuclear DNA fragmentation (3-fold increase; P<0.01) and selective activation of caspase 9 (P<0.05) and Bcl2-interacting mediator of cell death (Bim; 2- to 7-fold increase; P<0.05) in human diaphragm. MV also statistically significantly down-regulates mitochondrial gene expression and induces oxidative stress. In cultured muscle cells, we show that oxidative stress activates each of the catabolic pathways thought to underlie VIDD: apoptotic (P<0.05), proteasomal (P<0.05), and autophagic (P<0.01). Further, silencing Bim expression blocks (P<0.05) oxidative stress-induced apoptosis. Overlapping the gene expression profiles of MV human diaphragm and H₂O₂-treated muscle cells, we identify Fos, FoxO1, and Stat3 as regulators of Bim expression as well as of expression of the catabolic markers atrogin and LC3. We thus identify a novel Fos/FoxO1/Stat3-Bim intrinsic apoptotic pathway and establish the centrality of oxidative stress in the development of VIDD. This information may help in the design of specific drugs to prevent this condition.
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