Synthesis of hydroxy fatty acids from linoleic acid by human blood platelets

• Published in: Prostaglandins Vol. 38; no. 2; p. 203
• Main Authors: Daret, D, Blin, P, Larrue, J
• Format: Journal Article
• Language: English
• Published: United States 01-08-1989
• Subjects: Arachidonate 15-Lipoxygenase - metabolism; Arachidonate Lipoxygenases - metabolism; Arachidonic Acids - antagonists & inhibitors; Arachidonic Acids - metabolism; Blood Platelets - enzymology; Blood Platelets - metabolism; Chromatography, High Pressure Liquid; Humans; Hydroxyeicosatetraenoic Acids - biosynthesis; Indomethacin - pharmacology; Kinetics; Linoleic Acids - antagonists & inhibitors; Linoleic Acids - biosynthesis; Linoleic Acids - metabolism; Linoleic Acids, Conjugated; Prostaglandin-Endoperoxide Synthases - metabolism
• ISSN: 0090-6980
• DOI: 10.1016/0090-6980(89)90083-x

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.