Synthesis of hydroxy fatty acids from linoleic acid by human blood platelets.
The metabolism of linoleic acid by washed human platelets was investigated. [1.14C] linoleic acid was converted to [1.14C] hydroxy octadecadienoic acids (HODEs) at about the same rate with which [1.14C] 12-HETE was produced from [1.14C] arachidonic acid. The total radioactivity in HODEs was distributed among two isomers: 13-HODE (85%) and 9-HODE (15%) as defined by CG-MS. The production of HODEs by intact washed platelets was inhibited by indomethacin (IC50:5 x 10(-7) M) which suggest that hydroxy fatty acids were produced by PGH-synthase. By contrast, the production of HODEs by platelet cytosolic fractions was not modified under indomethacin treatment but completely abolished by NDGA (10(-3) M) and inhibited by the platelet lipoxygenase inhibitors 15-HETE (2.10(-5) M) and baicalein (10(-5) M). Platelets thus contain two different active systems which may convert linoleic acid to hydroxy fatty acids. Since these compounds remained essentially associated with the platelets, their presence may significantly participate in the mechanisms of platelet activation.
Daret
D
D
U. 8 Recherches Cardiologie, INSERM, Pessac, France.
Blin
P
P
Larrue
J
J
D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008041:Linoleic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D001091:Arachidonate Lipoxygenases; D001093:Arachidonate 15-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin