title: Hydroperoxides produced by n-6 lipoxygenation of arachidonic and linoleic acids potentiate synthesis of prostacyclin related compounds.
abstract: In a previous paper we reported that arachidonic acid (20:4(n-6] strongly enhances the endothelial cell synthesis of prostaglandin I3 (PGI3) from eicosapentaenoic acid (20:5(n-3], in stimulating the cyclooxygenase rather than the prostacyclin synthase (Bordet et al. (1986) Biochem. Biophys. Res. Commun. 135, 403-410). In the present study, endothelial cell monolayers were co-incubated with exogenous 20:5(n-3) or docosatetraenoic acid (22:4(n-6], and n-6 lipoxygenase products of 20:4(n-6) or linoleic acid (18:2(n-6], namely 15-HPETE and 13-HPOD, respectively. Prostaglandins or dihomoprostaglandins were then measured by gas chromatography-mass spectrometry. Both hydroperoxides, up to 20 microM, stimulated the cyclooxygenation of 20:5(n-3) and 22:4(n-6), in particular the formation of PGI3 and dihomo-PGI2, respectively. Higher concentrations inhibited prostacyclin synthetase. In contrast, the reduced products of hydroperoxides, 15-HETE and 13-HOD, failed to stimulate these cyclooxygenations, 13-HPOD appeared more potent than 15-HPETE and the cyclooxygenation of 22:4(n-6) seemed to require higher amounts of hydroperoxides to be efficiently metabolized than 20:5(n-3). These data suggest that prostacyclin potential of endothelium might be enhanced by raising the peroxide tone.
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000031:analogs & derivatives; D004883:Erucic Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D015289:Leukotrienes; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism* / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D013058:Mass Spectrometry; D011460:Prostaglandins F / Q000096:biosynthesis; D014471:Umbilical Veins
chemical_list: D001095:Arachidonic Acids; D004883:Erucic Acids; D005231:Fatty Acids, Unsaturated; D015289:Leukotrienes; D008041:Linoleic Acids; D008054:Lipid Peroxides; D011460:Prostaglandins F; C011395:adrenic acid; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C034240:prostaglandin I3; C054990:dihomo-prostaglandin I(2); D019787:Linoleic Acid; D011464:Epoprostenol; D008084:Lipoxygenase