Impairment of dolichyl saccharide synthesis and dolichol-mediated glycoprotein assembly in the aortic smooth muscle cell in culture by inhibitors of cholesterol biosynthesis.
25-Hydroxycholesterol treatment of the aortic smooth muscle cell inhibited the incorporation of acetate but not mevalonate into dolichol and cholesterol by 91 and 82%, respectively, and diminished the synthesis from glucose of cholesterol, dolichylpyrophosphoryl oligosaccharide, and dolichol-dependent glycoproteins. The dolichol-bound oligosaccharide unit contained approximately 10 Man/2 Glc/2 GlcNAc residues and appeared to be a precursor to protein-bound saccharide units which contained on the average 8 Man/1 Glc/2 GlcNAc residues. Mevalonate was found to protect the cells against the effect 25-hydroxycholesterol and to restore normal cellular synthesis of dolichyl saccharides and glycoproteins. It is suggested that hydroxymethylglutaryl coenzyme A reductase may function as a rate-controlling enzyme in the biosynthesis of not only sterols but also dolichols, and may as a result regulate the assembly of certain cellular glycoproteins.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D004224:Diterpenes / Q000378:metabolism*; D004286:Dolichols / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000378:metabolism; D011105:Polyisoprenyl Phosphate Sugars / Q000378:metabolism; D013261:Sterols / Q000494:pharmacology*
D000085:Acetates; D004224:Diterpenes; D004286:Dolichols; D006023:Glycoproteins; D006888:Hydroxycholesterols; D011105:Polyisoprenyl Phosphate Sugars; D013261:Sterols; D002784:Cholesterol; D008798:Mevalonic Acid