ArticlePloS one2013
12/15-Lipoxygenase-derived lipid metabolites induce retinal endothelial cell barrier dysfunction: contribution of NADPH oxidase.
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 55 papers.
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Who cites it
55 citing papers in PubMed, 94 citations in OpenAlex.
- Article
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- Systemic strategies to prevent early diabetic retinopathy: targeting polyunsaturated fatty acid metabolism and eicosanoid signaling.Frontiers in medicine · 2026Review
- Protocatechuic Acid Ameliorates Cisplatin-Induced Inflammation and Apoptosis in Mouse Proximal Tubular Cells.International journal of molecular sciences · 2025Article
- The Role of Diet and Oral Supplementation for the Management of Diabetic Retinopathy and Diabetic Macular Edema: A Narrative Review.BioMed research international · 2025Review
- Tempol, a Superoxide Dismutase Mimetic, Inhibits Wallerian Degeneration Following Spinal Cord Injury by Preventing Glutathione Depletion and Aldose Reductase Activation.Journal of neurotrauma · 2024Article
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- 12-HETE activates Müller glial cells: The potential role of GPR31 and miR-29.Prostaglandins & other lipid mediators · 2024Article
- Investigation of the Effects of a Novel NOX2 Inhibitor, GLX7013170, against Glutamate Excitotoxicity and Diabetes Insults in the Retina.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- Sustained activation of 12/15 lipoxygenase (12/15 LOX) contributes to impaired renal recovery post ischemic injury in male SHR compared to females.Molecular medicine (Cambridge, Mass.) · 2023Article
- Cardiovascular Effects of Environmental Metal Antimony: Redox Dyshomeostasis as the Key Pathogenic Driver.Antioxidants & redox signaling · 2023Review
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- Increased serum 12-hydroxyeicosatetraenoic acid levels are correlated with an increased risk of diabetic retinopathy in both children and adults with diabetes.Acta diabetologica · 2022Article
- Curcumin and Wnt/β‑catenin signaling in exudative age‑related macular degeneration (Review).International journal of molecular medicine · 2022Review
- Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.Life research · 2022Article
- A Hypothesis From Metabolomics Analysis of Diabetic Retinopathy: Arginine-Creatine Metabolic Pathway May Be a New Treatment Strategy for Diabetic Retinopathy.Frontiers in endocrinology · 2022Review
- Dapagliflozin Reduces Apoptosis of Diabetic Retina and Human Retinal Microvascular Endothelial Cells Through ERK1/2/cPLA2/AA/ROS Pathway Independent of Hypoglycemic.Frontiers in pharmacology · 2022Article
- Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration.Journal of inflammation research · 2022Review
- Oxidative and Nitrosative Stress in Age-Related Macular Degeneration: A Review of Their Role in Different Stages of Disease.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The purpose of the current study was to evaluate the effect of 12/15-lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to evaluate the effect of 12- and 15-hydroxyeicosatetreanoic acids (HETE) on REC permeability and transcellular electrical resistance (TER). Effect of 12- or 15-HETE on the levels of zonula occludens protein 1 (ZO-1), reactive oxygen species (ROS), NOX2, pVEGF-R2 and pSHP1 was examined in the presence or absence of inhibitors of NADPH oxidase. In vivo studies were performed using Ins2(Akita) mice treated with or without the 12/15-LOX inhibitor baicalein. Levels of HETE and inflammatory mediators were examined by LC/MS and Multiplex Immunoassay respectively. ROS generation and NOX2 expression were also measured in mice retinas. 12- and 15- HETE significantly increased permeability and reduced TER and ZO-1 expression in REC. VEGF-R2 inhibitor reduced the permeability effect of 12-HETE. Treatment of REC with HETE also increased ROS generation and expression of NOX2 and pVEGF-R2 and decreased pSHP1 expression. Treatment of diabetic mice with baicalein significantly decreased retinal HETE, ICAM-1, VCAM-1, IL-6, ROS generation, and NOX2 expression. Baicalein also reduced pVEGF-R2 while restored pSHP1 levels in diabetic retina. Our findings suggest that 12/15-LOX contributes to vascular hyperpermeability during DR via NADPH oxidase dependent mechanism which involves suppression of protein tyrosine phosphatase and activation of VEGF-R2 signal pathway.
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