ArticleThe Journal of biological chemistry2014
Vascular endothelial tight junctions and barrier function are disrupted by 15(S)-hydroxyeicosatetraenoic acid partly via protein kinase C ε-mediated zona occludens-1 phosphorylation at threonine 770/772.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 63 citations in OpenAlex.
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- Polymerase delta-interacting protein 2 mediates brain vascular permeability by regulating ROS-mediated ZO-1 phosphorylation and localization at the interendothelial border.Cell communication and signaling : CCS · 2025Article
- Regulating arachidonic acid metabolism: a novel strategy to prevent colorectal inflammatory cancer transformation.Journal of Cancer · 2025Review
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.Research square · 2024Article
- Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Plasma oxylipin profile of postpartum dairy cows categorized into different systemic inflammatory grades in the first week after parturition.JDS communications · 2024Article
- Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023Review
- The effect of circulating iron on barrier integrity of primary human endothelial cells.Scientific reports · 2023Article
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation.Journal of cellular and molecular medicine · 2022Article
- Growth State-Dependent Expression of Arachidonate Lipoxygenases in the Human Endothelial Cell Line EA.hy926.Cells · 2022Article
- Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects.Scientific reports · 2022Article
- Rosmarinic acid downregulates the oxLDL‑induced interaction between monocytes and endothelial cells, in addition to monocyte diapedesis, under high glucose conditions.International journal of molecular medicine · 2022Article
- Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity.International journal of molecular sciences · 2022Review
- PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer's Disease Hippocampus.Frontiers in aging neuroscience · 2022Article
Corrections and comments
- Correction · 2019-03-01Duplication of/in Image ·
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Disruption of tight junctions (TJs) perturbs endothelial barrier function and promotes inflammation. Previously, we have shown that 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1 (15-LO1) metabolite of arachidonic acid, by stimulating zona occludens (ZO)-2 tyrosine phosphorylation and its dissociation from claudins 1/5, induces endothelial TJ disruption and its barrier dysfunction. Here, we have studied the role of serine/threonine phosphorylation of TJ proteins in 15(S)-HETE-induced endothelial TJ disruption and its barrier dysfunction. We found that 15(S)-HETE enhances ZO-1 phosphorylation at Thr-770/772 residues via PKCε-mediated MEK1-ERK1/2 activation, causing ZO-1 dissociation from occludin, disrupting endothelial TJs and its barrier function, and promoting monocyte transmigration; these effects were reversed by T770A/T772A mutations. In the arteries of WT mice ex vivo, 15(S)-HETE also induced ZO-1 phosphorylation and endothelial TJ disruption in a PKCε and MEK1-ERK1/2-dependent manner. In line with these observations, in WT mice high fat diet feeding induced 12/15-lipoxygenase (12/15-LO) expression in the endothelium and caused disruption of its TJs and barrier function. However, in 12/15-LO(-/-) mice, high fat diet feeding did not cause disruption of endothelial TJs and barrier function. These observations suggest that the 12/15-LO-12/15(S)-HETE axis, in addition to tyrosine phosphorylation of ZO-2, also stimulates threonine phosphorylation of ZO-1 in the mediation of endothelial TJ disruption and its barrier dysfunction.
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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.