Inhibition of cholesterol biosynthesis by Delta22-unsaturated phytosterols via competitive inhibition of sterol Delta24-reductase in mammalian cells (original) (raw)

2002, The Biochemical journal

Dietary phytosterols are cholesterol-lowering agents that interfere with the intestinal absorption of cholesterol. In the present study, we have studied their effects on cholesterol biosynthesis in human cells, particularly in the sterol-conversion pathway. For this, both Caco-2 (intestinal mucosa) and HL-60 (promyelocytic) human cell lines were incubated with [(14)C]acetate, and the incorporation of radioactivity into sterols was determined using HPLC and radioactivity detection online. Sterols containing a double bond at C-22 in the side chain (stigmasterol, brassicasterol and ergosterol) dramatically inhibited the activity of sterol Delta(24)-reductase, as indicated by the decrease in radioactivity incorporation into cholesterol and the accumulation of its precursors (mainly desmosterol). Phytosterols with the saturated side chain (beta-sitosterol and campesterol) were inactive in this regard. The inhibition of sterol (24)-reductase was confirmed in rat liver microsomes by using ...