ArticleThe Journal of experimental medicine2000
Nitric oxide-dependent activation of p53 suppresses bleomycin-induced apoptosis in the lung.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 75 citations in OpenAlex.
- Role of Nitric Oxide Synthases in Respiratory Health and Disease: Insights from Triple Nitric Oxide Synthases Knockout Mice.International journal of molecular sciences · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Ficolin B secreted by alveolar macrophage exosomes exacerbates bleomycin-induced lung injury via ferroptosis through the cGAS-STING signaling pathway.Cell death & disease · 2023Article
- Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.The Journal of experimental medicine · 2021Article
- The regulation of nitric oxide in tumor progression and therapy.The Journal of international medical research · 2020Review
- Role of Melanin Chemiexcitation in Melanoma Progression and Drug Resistance.Frontiers in oncology · 2020Review
- p53: A Key Protein That Regulates Pulmonary Fibrosis.Oxidative medicine and cellular longevity · 2020Review
- In Vitro Anticancer Effect of Gedunin on Human Teratocarcinomal (NTERA-2) Cancer Stem-Like Cells.BioMed research international · 2017Article
- p53 predominantly regulates IL-6 production and suppresses synovial inflammation in fibroblast-like synoviocytes and adjuvant-induced arthritis.Arthritis research & therapy · 2016Article
- p53 and the Carcinogenicity of Chronic Inflammation.Cold Spring Harbor perspectives in medicine · 2016Review
- p53 protects against LPS-induced lung endothelial barrier dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- The Expression and Correlation of iNOS and p53 in Oral Squamous Cell Carcinoma.BioMed research international · 2015Article
- Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice.Respiratory research · 2014Article
- Regulation of lung injury and fibrosis by p53-mediated changes in urokinase and plasminogen activator inhibitor-1.The American journal of pathology · 2013Article
- Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor-1 for lung fibrosis.American journal of respiratory cell and molecular biology · 2012Article
- Transcription factor ets-2 plays an important role in the pathogenesis of pulmonary fibrosis.American journal of respiratory cell and molecular biology · 2011Article
- Inflammation and p53: A Tale of Two Stresses.Genes & cancer · 2011Article
- Pathologies associated with the p53 response.Cold Spring Harbor perspectives in biology · 2010Review
- Effect of nitric oxide donor and gamma irradiation on modifications of ERK and JNK in murine peritoneal macrophages.Journal of cell communication and signaling · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic inflammation leading to pulmonary fibrosis develops in response to environmental pollutants, radiotherapy, or certain cancer chemotherapeutic agents. We speculated that lung injury might be mediated by p53, a proapoptotic transcription factor widely implicated in the response of cells to DNA damage. Intratracheal administration of bleomycin led to caspase-mediated DNA fragmentation characteristic of apoptosis. The effects of bleomycin were associated with translocation of p53 from the cytosol to the nucleus only in alveolar macrophages that had been exposed to the drug in vivo, suggesting that the lung microenvironment regulated p53 activation. Experiments with a thiol antioxidant (N-acetylcysteine) in vivo and nitric oxide (NO) donors in vitro confirmed that reactive oxygen species were required for p53 activation. A specific role for NO was demonstrated in experiments with inducible nitric oxide synthase (iNOS)(-/)- macrophages, which failed to demonstrate nuclear p53 localization after in vivo bleomycin exposure. Strikingly, rates of bleomycin-induced apoptosis were at least twofold higher in p53(-/)- C57BL/6 mice compared with heterozygous or wild-type littermates. Similarly, levels of apoptosis were also twofold higher in the lungs of iNOS(-/)- mice than were observed in wild-type controls. Consistent with a role for apoptosis in chronic lung injury, levels of bleomycin-induced inflammation were substantially higher in iNOS(-/)- and p53(-/)- mice compared with wild-type controls. Together, our results demonstrate that iNOS and p53 mediate a novel apoptosis-suppressing pathway in the lung.
Indexed as
Identifiers
What OpenQuestion holds
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.