20-Hydroxyeicosatetraenoic Acid (20-HETE) Metabolism in Coronary Endothelial Cells
| Autor: | Terry L. Kaduce, Lynn M. Teesch, Arthur A. Spector, V. Raj Gopal, Kevin C. Dellsperger, Neal L. Weintraub, Shawn D. Harmon, John R. Falck, William B. Campbell, Christine L. Oltman, Xiang Fang |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Time Factors Endothelium Swine Biological Transport Active chemistry.chemical_element Vasodilation Biology Calcium Biochemistry chemistry.chemical_compound Phospholipase A2 Internal medicine Hydroxyeicosatetraenoic Acids medicine Animals Molecular Biology Calcimycin Ionophores Hydroxyeicosatetraenoic acid Cell Biology Metabolism 20-Hydroxyeicosatetraenoic acid Coronary Vessels medicine.anatomical_structure Endocrinology chemistry cardiovascular system biology.protein lipids (amino acids peptides and proteins) Arachidonic acid Endothelium Vascular |
| Zdroj: | Journal of Biological Chemistry. 279:2648-2656 |
| ISSN: | 0021-9258 |
| Popis: | We have investigated the role of endothelial cells in the metabolism of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive mediator synthesized from arachidonic acid by cytochrome P450 omega-oxidases. Porcine coronary artery endothelial cells (PCEC) incorporated 20-[(3)H]HETE primarily into the sn-2 position of phospholipids through a coenzyme A-dependent process. The incorporation was reduced by equimolar amounts of arachidonic, eicosapentaenoic or 8,9-epoxyeicosatrienoic acids, but some uptake persisted even when a 10-fold excess of arachidonic acid was available. The retention of 20-[(3)H]HETE increased substantially when methyl arachidonoyl fluorophosphonate, but not bromoenol lactone, was added, suggesting that a Ca(2+)-dependent cytosolic phospholipase A(2) released the 20-HETE contained in PCEC phospholipids. Addition of calcium ionophore A23187 produced a rapid release of 20-[(3)H]HETE from the PCEC, a finding that also is consistent with a Ca(2+)-dependent mobilization process. PCEC also converted 20-[(3)H]HETE to 20-carboxy-arachidonic acid (20-COOH-AA) and 18-, 16-, and 14-carbon beta-oxidation products. 20-COOH-AA produced vasodilation in porcine coronary arterioles, but 20-HETE was inactive. These results suggest that the incorporation of 20-HETE and its subsequent conversion to 20-COOH-AA in the endothelium may be important in modulating coronary vascular function. |
| Databáze: | OpenAIRE |
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