6533b872fe1ef96bd12d2ee8

RESEARCH PRODUCT

Effect of rat plasma high density lipoprotein with or without apolipoprotein E on the cholesterol uptake and on the induction of the corticosteroid biosynthetic pathway in newborn rat adrenocortical cell cultures

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Abstract High density lipoprotein (HDL) has been shown to induce the cellular accumulation of cholesterol esters and the biosynthesis of 21-hydroxysteroids (corticosteroids) newborn rat adrenocortical cells cultivated in serum-free medium. In order to identify the component(s) of HDL responsible for these effects, we investigated the ability of rat HDL subfractions and HDL with or without apolipoprotein E to deliver cholesterol to cells and to stimulate the steroid biosynthetic pathways in adrenal cultured cells. The total cholesterol uptake from HDL 2 was greater than that observed with HDL rich in apolipoprotein E (HDL 1 and HDL c ). Furthermore, the increase of the ratio between 21-hydroxysteroids and reductive metabolites of progesterone was higher with HDL 2 than with HDL 1 or HDL c . The results of competitive studies between LDL and HDL subfractions indicate that adrenal cells take up cholesterol from HDL 2 and LDL by separate mechanisms but that LDL and HDL containing apolipoprotein E share the same uptake processes. In experiments with various concentrations of HDL c or HDL without apolipoprotein E, the adrenal cells displayed a higher affinity for rat HDL c than for rat HDL without apolipoprotein E. However, HDL without apolipoprotein E produced a higher enhancement of the cholesterol cell content and was 3-fold more effective in stimulating 21-hydroxylated steroid production than rat HDL c . Although these findings suggest a participation of HDL with apolipoprotein E in the HDL interaction with rat adrenal cells, the predominant effect on these cells is devoluted to HDL containing mainly apolipoprotein A.