ArticlePloS one2013
Carbon monoxide abrogates ischemic insult to neuronal cells via the soluble guanylate cyclase-cGMP pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Attenuation of mitochondrial dysfunction in a ventricular fibrillation swine model of cardiac arrest treated with carbon monoxide.Resuscitation · 2025Article
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.PloS one · 2024Article
- Review
- Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?Antioxidants (Basel, Switzerland) · 2023Review
- Carbon monoxide signaling and soluble guanylyl cyclase: Facts, myths, and intriguing possibilities.Biochemical pharmacology · 2022Review
- Carbon Monoxide Modulation of Microglia-Neuron Communication: Anti-Neuroinflammatory and Neurotrophic Role.Molecular neurobiology · 2022Article
- Carbon monoxide and a change of heart.Redox biology · 2021Review
- Heme oxygenase‑1 improves the survival of ischemic skin flaps (Review).Molecular medicine reports · 2021Article
- Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).Frontiers in psychiatry · 2020Article
- P2X7 Receptors Mediate CO-Induced Alterations in Gene Expression in Cultured Cortical Astrocytes-Transcriptomic Study.Molecular neurobiology · 2019Article
- Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration.Neurobiology of disease · 2019Article
- Improvement of neuronal differentiation by carbon monoxide: Role of pentose phosphate pathway.Redox biology · 2018Article
- The Role of Gaseous Molecules in Traumatic Brain Injury: An Updated Review.Frontiers in neuroscience · 2018Review
- Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells.PloS one · 2018Article
- An Overview of the Potential Therapeutic Applications of CO-Releasing Molecules.Bioinorganic chemistry and applications · 2018Review
- The protective effects of carboxyhemoglobin during the resuscitation from hemorrhagic shock in rats.Oncotarget · 2017Article
- Review
- Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages.Frontiers in medicine · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCarbon monoxide (CO) is an accepted cytoprotective molecule. The extent and mechanisms of protection in neuronal systems have not been well studied. We hypothesized that delivery of CO via a novel releasing molecule (CORM) would impart neuroprotection in vivo against ischemia-reperfusion injury (IRI)-induced apoptosis of retinal ganglion cells (RGC) and in vitro of neuronal SH-SY5Y-cells via activation of soluble guanylate-cyclase (sGC).
methodsTo mimic ischemic respiratory arrest, SH-SY5Y-cells were incubated with rotenone (100 nmol/L, 4 h) ± CORM ALF186 (10-100 µmol/L) or inactivated ALF186 lacking the potential of releasing CO. Apoptosis and reactive oxygen species (ROS) production were analyzed using flow-cytometry (Annexin V, mitochondrial membrane potential, CM-H2DCFDA) and Western blot (Caspase-3). The impact of ALF186± respiratory arrest on cell signaling was assessed by measuring expression of nitric oxide synthase (NOS) and soluble guanylate-cyclase (sGC) and by analyzing cellular cGMP levels. The effect of ALF186 (10 mg/kg iv) on retinal IRI in Sprague-Dawley rats was assessed by measuring densities of fluorogold-labeled RGC after IRI and by analysis of apoptosis-related genes in retinal tissue.
resultsALF186 but not inactivated ALF186 inhibited rotenone-induced apoptosis (Annexin V positive cells: 25 ± 2% rotenone vs. 14 ± 1% ALF186+rotenone, p<0.001; relative mitochondrial membrane potential: 17 ± 4% rotenone vs. 55 ± 3% ALF186+rotenone, p<0.05). ALF186 increased cellular cGMP levels (33±5 nmol/L vs. 23±3 nmol/L; p<0.05) and sGC expression. sGC-inhibition attenuated ALF186-mediated protection (relative mitochondrial membrane potential: 55±3% ALF186+rotenone vs. 20 ± 1% ODQ + ALF186+rotenone, p<0.05). ALF186 protected RGC in vivo (IRI 1255 ± 327 RGC/mm(2) vs. ALF186 + IRI 2036 ± 83; p<0.05) while sGC inhibition abolished the protective effects of ALF186 (ALF186 + IRI 2036 ± 83 RGC/mm(2) vs. NS-2028 + ALF186 + IRI 1263 ± 170, p<0.05).
conclusionsThe CORM ALF186 inhibits IRI-induced neuronal cell death via activation of sGC and may be a useful treatment option for acute ischemic insults to the retina and the brain.
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