ArticleAmerican journal of physiology. Lung cellular and molecular physiology2010
Bleomycin induces the extrinsic apoptotic pathway in pulmonary endothelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions.Radiology and oncology · 2026Review
- The senescence-like activity of BMS-470539 is associated with anti-fibrotic actions in models of dermal fibrosis.Arthritis research & therapy · 2025Article
- Propranolol (1 mg/kg/day) with intralesional bleomycin versus propranolol monotherapy for infantile hemangioma: a randomized controlled trial.Frontiers in pharmacology · 2025Article
- Article
- Combination of Niclosamide and Pirfenidone Alleviates Pulmonary Fibrosis by Inhibiting Oxidative Stress and MAPK/Nf-κB and STATs Regulated Genes.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Blockade of caspase cascade overcomes malaria-associated acute respiratory distress syndrome in mice.Cell death & disease · 2022Article
- Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro.Cancers · 2021Article
- Bleomycin-Induced Lung Injury Increases Resistance to Influenza Virus Infection in a Type I Interferon-Dependent Manner.Frontiers in immunology · 2021Article
- TNF Signaling Dictates Myeloid and Non-Myeloid Cell Crosstalk to Execute MCMV-Induced Extrinsic Apoptosis.Viruses · 2020Article
- dSTORM microscopy evidences in HeLa cells clustered and scattered γH2AX nanofoci sensitive to ATM, DNA-PK, and ATR kinase inhibitors.Molecular and cellular biochemistry · 2020Article
- Classification and treatment of orbital venous malformations: an updated review.Frontiers of medicine · 2019Review
- Suboptimal extracellular pH values alter DNA damage response to induced double-strand breaks.FEBS open bio · 2018Article
- CaMKII inhibition in type II pneumocytes protects from bleomycin-induced pulmonary fibrosis by preventing Ca2+-dependent apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- DNA double-strand break repair is impaired in presenescent Syrian hamster fibroblasts.BMC molecular biology · 2015Article
- Protective and therapeutic effect of apocynin on bleomycin-induced lung fibrosis in rats.Inflammation · 2015Article
- Article
- Bleomycin-induced γH2AX foci map preferentially to replicating domains in CHO9 interphase nuclei.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2014Article
- Preventive effect of chrysin on bleomycin-induced lung fibrosis in rats.Inflammation · 2014Article
- Protective and therapeutic effect of molsidomine on bleomycin-induced lung fibrosis in rats.Inflammation · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Bleomycin, a chemotherapeutic agent, can cause pulmonary fibrosis in humans and is commonly used to induce experimental pulmonary fibrosis in rodents. In cell culture, bleomycin causes single- and double-stranded DNA breaks and produces reactive oxidative species, both of which require iron (Fe(2+)) and O(2). The mechanism of bleomycin-induced apoptosis is controversial due to its complexity. We investigated bleomycin apoptotic signaling events in primary pulmonary endothelial cells. Time course experiments revealed that bleomycin induced apoptosis within 4 h. Caspase-8, the initiator caspase for the extrinsic pathway, was activated within 2 h and preceded activation of the effector caspases-3 and -6 (4 h). Caspase-9, the initiator of the intrinsic pathway and release of cytochrome c from the mitochondria were not detected at these time points. Bleomycin induced the expression of Bcl-2 and Bcl-x(L), Bcl-2 family member proteins that protect cells from the mitochondria-dependent intrinsic apoptosis. Real-time quantitative RT-PCR results demonstrated that, at 4-8 h, bleomycin induced expression of TNF and TNF receptor family genes known to induce the extrinsic apoptotic pathway. Silencing of the death receptor adaptor protein Fas-associated death domain by short interfering RNA significantly reduced bleomycin-induced apoptosis. Apoptosis was also abrogated by caspase-8 inhibition, but only slightly reduced by caspase-3 inhibition. Together, these data suggest that bleomycin initiates apoptosis via the extrinsic pathway.
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Registered trials
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