NDLI: Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells.

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Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells.

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Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Capdevila, Jorge Harris, Raymond C. Chen, Jian-kang
Description	Author Affiliation: Chen JK ( Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.);
Abstract	In addition to its important functions in detoxification of foreign chemicals and biosynthesis of steroid hormones, the cytochrome P450 enzyme system metabolizes arachidonate to 14,15-epoxyeicosatrienoic acid (14,15-EET). This study demonstrates that a P450 arachidonate epoxygenase metabolite can activate cleavage of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and delineates an essential role for HB-EGF in the mitogenic effects of this lipid mediator. Blockade of HB-EGF processing or EGF receptor (EGFR) inhibited 14,15-EET-stimulated early mitogenic signals and DNA synthesis. 14,15-EET failed to induce mitogenesis in cell lines expressing minimal HB-EGF, whereas 14,15-EET induced soluble HB-EGF release into the conditioned media of cell lines that both express high levels of HB-EGF and display mitogenic response to this lipid mediator. Moreover, transfection of a bacterial 14,15-epoxygenase established intracellular endogenous 14,15-EET biosynthesis in cultured cell systems, which allowed direct confirmation of involvement of EGFR transactivation in the endogenous 14,15-EET-mediated mitogenic signaling pathway. This mechanism involves EET-dependent activation of metalloproteinases and release of the potent mitogenic EGFR ligand, HB-EGF.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cytochrome P-450 Enzyme System Metabolism Epidermal Growth Factor Physiology Epithelial Cells Oxygenases Phenylalanine Analogs & Derivatives Animals COS Cells Cell Line Cloning, Molecular DNA Biosynthesis Heparin-binding EGF-like Growth Factor Intercellular Signaling Peptides And Proteins Ligands Models, Biological Muscle, Smooth Cytology Pharmacology Phosphorylation Precipitin Tests Protein Binding Signal Transduction Swine Thiophenes Transcriptional Activation U937 Cells Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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