The prostacyclin analogue iloprost and prostaglandin E1 suppress sterol synthesis in freshly isolated human mononuclear leukocytes.
The effects of the stable prostacyclin analogue iloprost, prostaglandin E1 and prostaglandin F2 alpha on sterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a 3-fold rise in the rate of sterol synthesis from [14C]acetate or tritiated water. Iloprost and prostaglandin E1 added in increasing concentrations at zero time resulted in an inhibition of the synthesis of sterols, the suppression being 50 and 55% at a concentration of 1 mumol/1, respectively. Both prostaglandins yielded a sigmoidal log dose-effect curve. In contrast, prostaglandin F2 alpha had no influence on sterol synthesis up to a concentration of 1 mumol/1. The action of the prostacyclin analogue and prostaglandin E1 on the relative rate of sterol synthesis was not immediate, since the prostaglandins had no effect when given at 6 h to the incubation medium, and the incorporation of [14C]acetate into sterols was measured thereafter. The results suggest that prostacyclin and prostaglandin E1 affect cholesterol synthesis and therefore may play a role in the regulation of cellular cholesterol homeostasis and in the development of atherosclerosis.
Krone
W
W
Kaczmarczyk
P
P
Müller-Wieland
D
D
Greten
H
H
D000527:Alprostadil; D015237:Dinoprost; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D016285:Iloprost; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D013261:Sterols / Q000096:biosynthesis*; D013997:Time Factors
D011458:Prostaglandins E; D011460:Prostaglandins F; D013261:Sterols; D015237:Dinoprost; D011464:Epoprostenol; D000527:Alprostadil; D016285:Iloprost