Desialized Low‐Density Lipoprotein Regulates Cholesterol Metabolism in Receptor‐Deficient Fibroblasts

Abstract

Binding of homologous low density lipoproteins (LDL) to specific cell‐membrane receptors initiates regulation of cholesterol metabolism in normal human fibroblasts, but minor regulatory effects are observed in receptor‐deficient cells. After enzymic removal of sialic acid residues, however, the desialized LDL aquires the ability to regulate cholesterol biosynthesis and cholesterol esterification in receptor‐deficient cells as effective as native LDL in normal cells. This is indicated by a suppression of hydroxymethylglutaryl‐CoA reductase activity, by a reduced incorporation of [14C]acetate into cholesterol and by a stimulation of the [3H]oleate incorporation into cholesterol esters in both normal and receptor deficient cells. Competitive binding and internalisation experiments revealed that the action of desialized LDL in normal and receptor‐deficient cells is receptor‐specific.The results suggest that desialisation of LDL facilitates its binding to cell membrane receptors, its internalisation and subsequent regulation of cellular cholesterol metabolism, this effect becoming significant in fibroblasts with reduced number of LDL receptors.