Effects of oxysterols on arachidonic acid metabolism and prostacyclin synthesis in bovine aortic smooth muscle cells in culture.
Previous studies have shown that oxysterols could induce arterial damage in animals and manifest potent toxicity in cultured cells. Bovine aortic smooth muscle cells in culture were used to study the effects of several cholesterol oxides on arachidonic acid (AA) metabolism. Using two different methods, i.e. radioactive labeling of cells with 14C-AA and radioimmunoassay of 6kPGF1 alpha, the stable metabolite of Prostacyclin (PGI2), we observed various effects depending on the substance. Oxysterols oxidised on the rings were able to inhibit AA metabolism only at high doses, toxic to the cells, presumably through a non specific lytic mechanism. Oxysterols oxidised on the side chain induced an inhibition of the overall arachidonate conversion and PGI2 synthesis at low doses, below the range of cytotoxicity. This inhibition was noted both on the basal and stimulated metabolism. Mechanisms involved in such actions are still to be determined.
Seilan
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C
INRA-Laboratoire des Sciences de la Consommation, Jouy en Josas, France.
Dubuquoy
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C
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives*; D011464:Epoprostenol / Q000096:biosynthesis*; D006888:Hydroxycholesterols / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D013261:Sterols / Q000494:pharmacology*
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D006888:Hydroxycholesterols; D013261:Sterols; C003585:22-hydroxycholesterol; C025813:20-hydroxycholesterol; D015121:6-Ketoprostaglandin F1 alpha; D002784:Cholesterol; D011464:Epoprostenol