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Docosatetraenoic acid in endothelial cells: formation, retroconversion to arachidonic acid, and effect on prostacyclin production
Authors:C J Mann  T L Kaduce  P H Figard  A A Spector
Institution:1. Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China;2. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China;3. Key Laboratory of Marine Geology and Environment, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China;1. School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212018, China;2. Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212018, China;1. Department of Biological Sciences, National University of Singapore, Kent Ridge, Singapore 117543, Republic of Singapore;2. St. John''s Island National Marine Laboratory, National University of Singapore, 18 Kent Ridge Road, Singapore 119227, Republic of Singapore;3. Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Republic of Singapore;4. The Tropical Marine Science Institute, National University of Singapore, Kent Ridge, Singapore 119227, Republic of Singapore;1. Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo, Japan;2. Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan;3. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan;4. Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan;5. Next Generation Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa, Japan;6. Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan
Abstract:Cultured bovine aortic endothelial cells convert arachidonic acid to docosatetraenoic acid and also take up docosatetraenoic acid from the extracellular fluid. After a 24-h incubation with biosynthetically prepared 3H]docosatetraenoic acid, about 20% of the cellular fatty acid radioactivity was converted to arachidonic acid. Furthermore, in pulse-chase experiments, the decrease in phospholipid docosatetraenoic acid content was accompanied by an increase in arachidonic acid, providing additional evidence for retroconversion. These findings suggest that one possible function of docosatetraenoic acid in endothelial cells is to serve as a source of arachidonic acid. The endothelial cells can release docosatetraenoic acid when they are stimulated with ionophore A23187, but they do not form appreciable amounts of eicosanoids from docosatetraenoic acid. Enrichment of the endothelial cells with docosatetraenoic acid reduced their capacity to produce prostacyclin (PGI2) in response to ionophore A23187. This may be related to the fact that docosatetraenoic acid enrichment caused a 40% reduction in the arachidonic acid content of the inositol phosphoglycerides. In addition, less prostacyclin was formed when the enriched cells were incubated with arachidonic acid, suggesting that docosatetraenoic acid also may act as an inhibitor of prostaglandin synthesis in endothelial cells.
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