ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04445285 (Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure), which is not on this map. Cited by 32 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure
Who cites it
32 citing papers in PubMed.
- Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects.Annals of surgery · 2013Trial
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Multidimensional study on mitochondrial dysfunction in pulmonary hypertension.Frontiers in medicine · 2025Review
- Racing against time: leveraging preclinical models to understand pulmonary susceptibility to perinatal acetaminophen exposures.American journal of physiology. Lung cellular and molecular physiology · 2022Review
- The proteomic response is linked to regional lung volumes in ventilator-induced lung injury.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Mitochondrial dysfunction in lung ageing and disease.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Mitochondrial Dysfunction: Metabolic Drivers of Pulmonary Hypertension.Antioxidants & redox signaling · 2019Review
- Roles of OGG1 in transcriptional regulation and maintenance of metabolic homeostasis.DNA repair · 2019Review
- Low-power laser alters mRNA levels from DNA repair genes in acute lung injury induced by sepsis in Wistar rats.Lasers in medical science · 2019Article
- Enhanced mitochondrial DNA repair of the common disease-associated variant, Ser326Cys, of hOGG1 through small molecule intervention.Free radical biology & medicine · 2018Article
- Mechanical ventilation and Streptococcus pneumoniae pneumonia alter mitochondrial homeostasis.Scientific reports · 2018Article
- Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.American journal of physiology. Lung cellular and molecular physiology · 2018Review
- A novel mtDNA repair fusion protein attenuates maladaptive remodeling and preserves cardiac function in heart failure.American journal of physiology. Heart and circulatory physiology · 2018Article
- Mitochondrial damage pathways in ventilator induced lung injury (VILI): an update.Journal of lung health and diseases · 2018Article
- Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes.Cell transplantation · 2017Article
- Impact of a novel phosphoinositol-3 kinase inhibitor in preventing mitochondrial DNA damage and damage-associated molecular pattern accumulation: Results from the Biochronicity Project.The journal of trauma and acute care surgery · 2017Article
- Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?Journal of cancer research and clinical oncology · 2017Review
- Pharmacologic Protection of Mitochondrial DNA Integrity May Afford a New Strategy for Suppressing Lung Ischemia-Reperfusion Injury.Annals of the American Thoracic Society · 2017Review
- Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.Shock (Augusta, Ga.) · 2017Article
- DNA damage related crosstalk between the nucleus and mitochondria.Free radical biology & medicine · 2017Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
This study tested the hypothesis that oxidative mitochondrial-targeted DNA (mtDNA) damage triggered ventilator-induced lung injury (VILI). Control mice and mice infused with a fusion protein targeting the DNA repair enzyme, 8-oxoguanine-DNA glycosylase 1 (OGG1) to mitochondria were mechanically ventilated with a range of peak inflation pressures (PIP) for specified durations. In minimal VILI (1 h at 40 cmH(2)O PIP), lung total extravascular albumin space increased 2.8-fold even though neither lung wet/dry (W/D) weight ratios nor bronchoalveolar lavage (BAL) macrophage inflammatory protein (MIP)-2 or IL-6 failed to differ from nonventilated or low PIP controls. This increase in albumin space was attenuated by OGG1. Moderately severe VILI (2 h at 40 cmH(2)O PIP) produced a 25-fold increase in total extravascular albumin space, a 60% increase in W/D weight ratio and marked increases in BAL MIP-2 and IL-6, accompanied by oxidative mitochondrial DNA damage, as well as decreases in the total tissue glutathione (GSH) and GSH/GSSH ratio compared with nonventilated lungs. All of these injury indices were attenuated in OGG1-treated mice. At the highest level of VILI (2 h at 50 cmH(2)O PIP), OGG1 failed to protect against massive lung edema and BAL cytokines or against depletion of the tissue GSH pool. Interestingly, whereas untreated mice died before completing the 2-h protocol, OGG1-treated mice lived for the duration of observation. Thus mitochondrially targeted OGG1 prevented VILI over a range of ventilation times and pressures and enhanced survival in the most severely injured group. These findings support the concept that oxidative mtDNA damage caused by high PIP triggers induction of acute lung inflammation and injury.
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Registered trials
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