Mechanism for endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid, an arachidonate lipoxygenase product.
The mechanisms for endothelial cell injury induced by the lipid hydroperoxide 15-hydroperoxyeicosatetraenoic acid (15-HPETE), an arachidonate lipoxygenase product, were explored in cultured bovine endothelial cells. In serum-free medium, there was significant incorporation of [3H]-15-HPETE into the phospholipids of endothelial monolayers, and 15-HPETE induced severe endothelial cell injury, which was determined by the 51Cr-release assay. In contrast, in serum containing medium, there was little incorporation of [3H]-15-HPETE into the cells, and no cellular injury occurred. In the serum free condition, [3H]-15-HPETE was mainly incorporated into the phospholipids. The incorporated 15-HPETE produced lipid peroxidation, which was determined by the accumulation of malondialdehyde in the cells. The 15-HPETE-induced lipid peroxidation was suppressed by radical scavengers (MK-447, MCI-186), anti-oxidants (alpha-tocopherol, butylated hydroxytoluene) and iron chelators (desferrioxamine,2,2'-bipyridine). Furthermore, these agents also suppressed the 15-HPETE-induced cytotoxicity. These results indicate that 15-HPETE-induced endothelial cell injury depends on iron-mediated lipid peroxidation.
Ochi
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H
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
Morita
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Murota
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D002417:Cattle; D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008315:Malondialdehyde / Q000032:analysis; D010743:Phospholipids / Q000378:metabolism
D000975:Antioxidants; D016895:Culture Media, Serum-Free; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008054:Lipid Peroxides; D010743:Phospholipids; D008315:Malondialdehyde; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases