Transformation of 15-Hydroperoxyeicosapentaenoic Acid Into Mono-and Dihydroxyeicosapentaenoic Acids by Human Platelets
[1-14C]-15-hydroperoxyeicosapentaenoic acid was incubated with suspensions of washed human platelets. Two dihydroxy and one monohydroxy metabolites were isolated and purified by RP-HPLC and SPHPLC. GC/MS analysis revealed that the three metabolites were: 8,15-dihydroxyeicosapentaenoic acid, 14,15-dihydroxyeicosapentaenoic acid and 15-hydroxyeicosapentaenoic acid. In addition, the non-enzymatic generation of an allylic hydroxy-epoxide metabolite (13-hydroxy-14,15-epoxyeicosapentaenoic acid) was identified. Furthermore, 15-HEPE was demonstrated to be a potent inhibitor of fMLP-induced neutrophil aggregation. Thus, transformation of the 15-lipoxygenase product of eicosapentaenoic acid by platelets may generate biologically active compounds that modulate neutrophil function.
KeywordsMethyl Ester Eicosapentaenoic Acid Human Platelet Neutrophil Aggregation Soybean Lipoxygenase
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