ArticleInvestigative ophthalmology & visual science2016
A Novel Inhibitor of 5-Lipoxygenase (5-LOX) Prevents Oxidative Stress-Induced Cell Death of Retinal Pigment Epithelium (RPE) Cells.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanistic insights into the role of PEDF-R (PNPLA2) in photoreceptors.Bioscience reports · 2026Review
- Emerging Roles and Possible Therapeutic Applications of Arachidonic Acid Metabolites in Sepsis and Sepsis-Associated Organ Dysfunction.Drug design, development and therapy · 2026Review
- Synthesis and Molecular Modeling of Antioxidant and Anti-Inflammatory Five-Membered Heterocycle-Cinnamic Acid Hybrids.Molecules (Basel, Switzerland) · 2025Article
- Article
- Inhibition of CysLTR1 reduces the levels of aggregated proteins in retinal pigment epithelial cells.Scientific reports · 2023Article
- Hydrogen peroxide-induced oxidative damage and protective role of peroxiredoxin 6 protein via EGFR/ERK signaling pathway in RPE cells.Frontiers in aging neuroscience · 2023Article
- An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration inAntioxidants (Basel, Switzerland) · 2022Article
- Dependence of Retinal Pigment Epithelium Integrity on the NRF2-Heme Oxygenase-1 Axis.Investigative ophthalmology & visual science · 2022Article
- Curcumin and Wnt/β‑catenin signaling in exudative age‑related macular degeneration (Review).International journal of molecular medicine · 2022Review
- 5-Lipoxygenase Inhibition Protects Retinal Pigment Epithelium from Sodium Iodate-Induced Ferroptosis and Prevents Retinal Degeneration.Oxidative medicine and cellular longevity · 2022Article
- Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration.Journal of inflammation research · 2022Review
- Article
- Degradation of Photoreceptor Outer Segments by the Retinal Pigment Epithelium Requires Pigment Epithelium-Derived Factor Receptor (PEDF-R).Investigative ophthalmology & visual science · 2021Article
- Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels.International journal of molecular sciences · 2021Review
- Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells.Scientific reports · 2020Article
- Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization.Oxidative medicine and cellular longevity · 2020Review
- PEDF protects human retinal pigment epithelial cells against oxidative stress via upregulation of UCP2 expression.Molecular medicine reports · 2019Article
- Role of the PNPLA2 Gene in the Regulation of Oxidative Stress Damage of RPE.Advances in experimental medicine and biology · 2019Article
- Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models.JCI insight · 2018Article
- Over-expression of CNTF in bone marrow mesenchymal stem cells protects RPE cells from short-wavelength, blue-light injury.In vitro cellular & developmental biology. Animal · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purpose5-Lipoxygenase (5-LOX) oxygenates arachidonic acid to form 5-hydroperoxyeicosatetraenoic acid, which is further converted into biologically detrimental leukotrienes, such as leukotriene B4 (LTB4). The RPE and retina express the PNPLA2 gene for pigment epithelium-derived factor receptor (PEDF-R), a lipase involved in cell survival. The purpose here was to investigate the role of PEDF-R on the 5-LOX pathway in oxidative stress of RPE.
methodsLipoxygenase activity assays were performed with soybean and potato lipoxygenase. Binding was evaluated by peptide-affinity chromatography and pull-down assays with PEDF-R-derived synthetic peptides or recombinant protein. Oxidative stress was induced in human ARPE-19 and primary pig RPE cells with indicated concentrations of H2O2/TNF-α. Reverse transcription-PCR of ALOX5 and PNPLA2 genes was performed. Cell viability and death rates were determined using respective biomarkers. Leukotriene B4 levels were measured by ELISA.
resultsAmong five peptides spanning between positions Leu159 and Met325 of human PEDF-R polypeptide, only two overlapping peptides, E5b and P1, bound and inhibited lipoxygenase activity. Human recombinant 5-LOX bound specifically to peptide P1 and to His6/Xpress-tagged PEDF-R via ionic interactions. The two inhibitor peptides E5b and P1 promoted cell viability and decreased cell death of RPE cells undergoing oxidative stress. Oxidative stress decreased the levels of PNPLA2 transcripts with no effect on ALOX5 expression. Exogenous additions of P1 peptide or overexpression of the PNPLA2 gene decreased both LTB4 levels and death of RPE cells undergoing oxidative stress.
conclusionsA novel peptide region of PEDF-R inhibits 5-LOX, which intersects with RPE cell death pathways induced by oxidative stress.
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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.