ArticleThe Journal of biological chemistry2011
Activation of cytosolic phospholipase A2 downstream of the Src-phospholipase D1 (PLD1)-protein kinase C γ (PKCγ) signaling axis is required for hypoxia-induced pathological retinal angiogenesis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Hypoxia-Induced Inflammation in In Vitro Model of Human Blood-Brain Barrier: Modulatory Effects of the Olfactory Ensheathing Cell-Conditioned Medium.Molecular neurobiology · 2025Article
- Silver Nanoparticles Cause Neural and Vascular Disruption by Affecting Key Neuroactive Ligand-Receptor Interaction and VEGF Signaling Pathways.International journal of nanomedicine · 2023Article
- Vascular Endothelial Growth Factor: A Translational View in Oral Non-Communicable Diseases.Biomolecules · 2021Review
- Aldolase A and Phospholipase D1 Synergistically Resist Alkylating Agents and Radiation in Lung Cancer.Frontiers in oncology · 2021Article
- Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy.International journal of molecular sciences · 2020Article
- LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function.BMC genomics · 2020Article
- Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure.Frontiers in physiology · 2018Article
- Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment.Journal of lipid research · 2016Article
- BK Induces cPLA2 Expression via an Autocrine Loop Involving COX-2-Derived PGE2 in Rat Brain Astrocytes.Molecular neurobiology · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling pathways in different cell types in the central nervous system.Molecular neurobiology · 2014Review
- Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK.PloS one · 2014Article
- Article
- Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis.Science signaling · 2012Article
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7 authors.
Funding
Abstract
In view of understanding the mechanisms of retinal neovascularization, we had reported previously that vascular endothelial growth factor (VEGF)-induced pathological retinal angiogenesis requires the activation of Src-PLD1-PKCγ signaling. In the present work, we have identified cytosolic phospholipase A(2) (cPLA(2)) as an effector molecule of Src-PLD1-PKCγ signaling in the mediation of VEGF-induced pathological retinal angiogenesis based on the following observations. VEGF induced cPLA(2) phosphorylation in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). VEGF also induced arachidonic acid (AA) release in a dose-, time-, and cPLA(2)-dependent manner. Depletion of cPLA(2) levels inhibited VEGF-induced HRMVEC DNA synthesis, migration, and tube formation. In addition, the exogenous addition of AA rescued VEGF-induced HRMVEC DNA synthesis, migration, and tube formation from inhibition by down-regulation of cPLA(2). Inhibition of Src, PLD1, or PKCγ attenuated VEGF-induced cPLA(2) phosphorylation and AA release. Consistent with these findings, hypoxia induced cPLA(2) phosphorylation and activity in VEGF-Src-PLD1-PKCγ-dependent manner in a mouse model of oxygen-induced retinopathy. In addition, siRNA-mediated down-regulation of cPLA(2) levels in the retina abrogated hypoxia-induced retinal endothelial cell proliferation and neovascularization. These observations suggest that cPLA(2)-dependent AA release is required for VEGF-induced Src-PLD1-PKCγ-mediated pathological retinal angiogenesis.
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