ArticleThe Journal of experimental medicine2000
Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis.
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 314 papers.
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Who cites it
314 citing papers in PubMed, 978 citations in OpenAlex.
- Low Dose Carbon Monoxide Exposure in Idiopathic Pulmonary Fibrosis Produces a CO Signature Comprised of Oxidative Phosphorylation Genes.Scientific reports · 2019Trial
- Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.Redox report : communications in free radical research · 2026Review
- A human two-hit platform modeling post-ischemic sterile inflammation and diastolic dysfunction in hiPSC-derived cardiac models.Materials today. Bio · 2026Article
- Harnessing endogenous carbon monoxide for cancer-selective drug synthesis.Nature communications · 2026Article
- HB reduces inflammation in HUVECs via the Nrf2/HO-1 axis by inhabiting apoptosis and oxidative stress.Scientific reports · 2026Article
- When Red Blood Cells Meet Carbon Monoxide: Yin and Yang in Medicines and Pharmaceuticals.Pharmaceuticals (Basel, Switzerland) · 2026Review
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- The molecular mechanisms of gas signaling molecules in bronchopulmonary dysplasia related lung injury.Frontiers in cell and developmental biology · 2026Review
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- Heme oxygenase-1 activation in mononuclear phagocytes in acute Kawasaki disease.Frontiers in pediatrics · 2026Article
- Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy.Biological procedures online · 2025Article
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review.Clinical science (London, England : 1979) · 2025Review
- Article
- Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction.International journal of molecular sciences · 2024Review
- Heme Oxygenase-1 and Prostate Cancer: Function, Regulation, and Implication in Cancer Therapy.International journal of molecular sciences · 2024Review
- The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.Cancer cell international · 2024Article
- Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration.International journal of molecular sciences · 2024Review
- JunB condensation attenuates vascular endothelial damage under hyperglycemic condition.Journal of molecular cell biology · 2024Article
- On the Question of CO's Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources.ACS chemical biology · 2024Article
254 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-alpha. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO.
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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.