ArticleMolecular and cellular biology2007
Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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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
16 citing papers in PubMed, 34 citations in OpenAlex.
- General View of Arachidonic Acid (AA) Metabolism.Reviews of physiology, biochemistry and pharmacology · 2027Review
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- The metabolic landscape of tomato roots during arbuscular mycorrhizal symbiosis reveals lipid-related metabolic rewiring.Plant cell reports · 2025Article
- Preliminary Proteomic and Metabolomic Analyses Reveal Potential Serum Biomarkers for Identifying Alveolar Echinococcosis in Mice.Veterinary sciences · 2025Article
- Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney.Journal of the American Society of Nephrology : JASN · 2016Article
- Phosphatidylinositol 3-kinase signaling determines kidney size.The Journal of clinical investigation · 2015Article
- Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism.Biochimica et biophysica acta · 2015Review
- Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway.Molecular and cellular biology · 2012Article
- EGFR signaling promotes TGFβ-dependent renal fibrosis.Journal of the American Society of Nephrology : JASN · 2012Article
- Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways.Chemical reviews · 2011Review
- Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications.Pharmacological reviews · 2010Review
- Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent transforming growth factor-alpha shedding.Molecular biology of the cell · 2009Article
- 14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates containing epoxide bioisosteres: influence upon vascular relaxation and soluble epoxide hydrolase inhibition.Journal of medicinal chemistry · 2009Article
- Arachidonic acid cytochrome P450 epoxygenase pathway.Journal of lipid research · 2009Review
- Identification of novel endogenous cytochrome p450 arachidonate metabolites with high affinity for cannabinoid receptors.The Journal of biological chemistry · 2008Article
- The complications of promiscuity: endocannabinoid action and metabolism.British journal of pharmacology · 2007Review
Corrections and comments
- Erratum issuedGuthi, Jagadeesh Setti [added]
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Arachidonic acid is an essential constituent of cell membranes that is esterified to the sn-2 position of glycerophospholipids and is released from selected phospholipid pools by tightly regulated phospholipase cleavage. Metabolism of the released arachidonic acid by the cytochrome P450 enzyme system (cP450) generates biologically active compounds, including epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids. Here we report that 2-(14,15-epoxyeicosatrienoyl)glycerol (2-14,15-EG), a novel cP450 arachidonate metabolite produced in the kidney, is a potent mitogen for renal proximal tubule cells. This effect is mediated by activation of tumor necrosis factor alpha-converting enzyme (ADAM17), which cleaves membrane-bound transforming growth factor alpha (proTGF-alpha) and releases soluble TGF-alpha as a ligand that binds and activates epidermal growth factor receptor (EGFR). The present studies additionally demonstrate that the structurally related 14,15-EET stimulates release of soluble heparin-binding EGF-like growth factor as an EGFR ligand by activation of ADAM9, another member of the ADAM family. Thus, in addition to the characterization of 2-14,15-EG's mitogenic activity and signaling mechanism, our study provides the first example that two structurally related biologically active lipid mediators can activate different metalloproteinases and release different EGFR ligands in the same cell type to activate EGFR and stimulate cell proliferation.
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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.