ArticlePloS one2016
The CORM ALF-186 Mediates Anti-Apoptotic Signaling via an Activation of the p38 MAPK after Ischemia and Reperfusion Injury in Retinal Ganglion Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Pooled it
- Expression Profiling of Exosomal miRNAs Derived from the Peripheral Blood of Kidney Recipients with DGF Using High-Throughput Sequencing.BioMed research international · 2019Trial
- Carbon Monoxide Therapy: Evidence and Prospects for Preventing and Treating Retinal Diseases.Biomolecules · 2026Review
- Carbon monoxide potentiates the effect of corticosteroids in suppressing inflammatory responses in cell culture.Bioorganic & medicinal chemistry · 2025Article
- Tetramethylpyrazine protects mitochondrial function by up-regulation of TFAM and inhibition of neuronal apoptosis in a rat model of surgical brain injury.Iranian journal of basic medical sciences · 2024Article
- Review
- Regulated Cell Death of Retinal Ganglion Cells in Glaucoma: Molecular Insights and Therapeutic Potentials.Cellular and molecular neurobiology · 2023Review
- Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?Antioxidants (Basel, Switzerland) · 2023Review
- Carbon Monoxide-Releasing Molecule-3 Enhances Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells via miR-195-5p/Wnt3a Pathway.Drug design, development and therapy · 2022Article
- Carbon Monoxide-Releasing Molecule-3 Regulates the Polarization of Lipopolysaccharide-Induced Macrophages.Inflammation · 2021Article
- 5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis.FEBS open bio · 2019Article
- Carbon monoxide in lung cell physiology and disease.American journal of physiology. Cell physiology · 2018Review
- Sinomenine reduces neuronal cell apoptosis in mice after traumatic brain injury via its effect on mitochondrial pathway.Drug design, development and therapy · 2018Article
- Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIschemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage.
methodsIRI was performed in rat´s retinae for 1 hour. The water-soluble CORM ALF-186 (10 mg/kg) was administered intravenously via a tail vein after reperfusion. After 24 and 48 hours, retinal tissue was harvested to analyze mRNA and protein expression of Bcl-2, Bax, Caspase-3, ERK1/2, p38 and JNK. Densities of fluorogold pre-labeled retinal ganglion cells (RGC) were analyzed 7 days after IRI. Immunohistochemistry was performed on retinal cross sections.
resultsALF-186 significantly reduced IRI mediated loss of RGC. ALF-186 treatment differentially affected mitogen-activated protein kinases (MAPK) phosphorylation: ALF-186 activated p38 and suppressed ERK1/2 phosphorylation, while JNK remained unchanged. Furthermore, ALF-186 treatment affected mitochondrial apoptosis, decreasing pro-apoptotic Bax and Caspase-3-cleavage, but increasing anti-apoptotic Bcl-2. Inhibition of p38-MAPK using SB203580 reduced ALF-186 mediated anti-apoptotic effects.
conclusionIn this study, ALF-186 mediated substantial neuroprotection, affecting intracellular apoptotic signaling, mainly via MAPK p38. CORMs may thus represent a promising therapeutic alternative treating neuronal IRI.
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