ArticleThe Journal of biological chemistry2009
Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 105 citations in OpenAlex.
- Circulating Protectin D1 and Neutrophils Extracellular Traps in the Diagnosis and Progression of Acute Pancreatitis.Journal of inflammation research · 2024Trial
- The serum levels of polyunsaturated fatty acids contribute to the antidepressant-like effects of 18β-Glycyrrhetinic acid in mice.Psychopharmacology · 2025Article
- The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases.Current neuropharmacology · 2025Review
- Autosomal-dominant macular dystrophy linked to a chromosome 17 tandem duplication.JCI insight · 2024Article
- (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.International journal of molecular sciences · 2024Article
- Impact of dietary changes on retinal neuronal plasticity in rodent models of physical and psychological trauma.Frontiers in genetics · 2024Article
- cRel and Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets for Neuroprotection.Cellular and molecular neurobiology · 2023Article
- Resolution of Inflammation in Retinal Disorders: Briefly the State.International journal of molecular sciences · 2022Review
- New Retinal Pigment Epithelial Cell Model to Unravel Neuroprotection Sensors of Neurodegeneration in Retinal Disease.Frontiers in neuroscience · 2022Article
- Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment.Nutrients · 2021Review
- Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Fair-Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration.Molecular nutrition & food research · 2020Review
- Article
- Remodeling of Substance P Sensory Nerves and Transient Receptor Potential Melastatin 8 (TRPM8) Cold Receptors After Corneal Experimental Surgery.Investigative ophthalmology & visual science · 2019Article
- Proresolving Lipid Mediators: Endogenous Modulators of Oxidative Stress.Oxidative medicine and cellular longevity · 2019Review
- Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection.Molecular aspects of medicine · 2018Review
- Dietary DHA amplifies LXAMucosal immunology · 2018Article
- Characterization of Epidermal Lipoxygenase Expression in Normal Human Skin and Tissue-Engineered Skin Substitutes.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Retinal Pigment Epithelium and Photoreceptor Preconditioning Protection Requires Docosanoid Signaling.Cellular and molecular neurobiology · 2018Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The integrity of the retinal pigment epithelial (RPE) cell is essential for the survival of rod and cone photoreceptor cells. Several stressors, including reactive oxygen species, trigger apoptotic damage in RPE cells preceded by an anti-inflammatory, pro-survival response, the formation of neuroprotectin D1 (NPD1), an oxygenation product derived from the essential omega-3 fatty acid family member docosahexaenoic acid. To define the ability of NPD1 and other endogenous novel lipid mediators in cell survival, we generated a stable knockdown human RPE (ARPE-19) cell line using short hairpin RNA to target 15-lipoxygenase-1. The 15-lipoxygenase-1-deficient cells exhibited 30% of the protein expression, and 15-lipoxygenase-2 remained unchanged, as compared with an ARPE-19 cell line control established using nonspecific short hairpin RNA transfected cells. NPD1 synthesis was stimulated by tumor necrosis factor alpha/H2O2-mediated oxidative stress in nonspecific cells (controls), whereas in silenced cells, negligible amounts of NPD1, 12(S)- and 15(S)-hydroxyeicosatetraenoic acid, and lipoxin A4 were found under these conditions. Neither control nor the deficient cells showed an increase in 15-lipoxygenase-1 protein content after 16 h of oxidative stress, suggesting that the increased activity of 15-lipoxygenase-1 is due to activation of pre-existing proteins. 15-Lipoxygenase-silenced cells also displayed an exacerbated sensitivity to oxidative stress-induced apoptosis when compared with the control cells. NPD1 selectively and potently rescued 15-lipoxygenase-silenced cells from oxidative stress-induced apoptosis. These results demonstrate that 15-lipoxygenase-1 is activated by oxidative stress in ARPE-19 cells and that NPD1 is part of an early survival signaling in RPE cells.
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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.