Inhibition of Scavenger Receptor-Mediated Modified Low-Density Lipoprotein Endocytosis in Cultured Bovine Aortic Endothelial Cells by the Glycoprotein Processing Inhibitor Castanospermine

Eugene A. Sprague, Ravi Kothapalli, Alan D. Elbein, James J. Kerbacher, Ellen H. Edwards, Alan D. Elbein, Colin J. Schwartz

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizidine) is a plant alkaloid that inhibits α-glucosidases, including the glycoprotein processing glucosidase I. When endothelial cells were grown for 48 h, or longer, in the presence of this alkaloid, they produced scavenger receptors for modified low-density lipoproteins (LDL) that had mostly Glc3Man7–9(GlcNAc)2 structures rather than the usual complex types of oligosaccharides. Furthermore, growth in the presence of castanospermine resulted in a substantial inhibition in degradation of endocytosed 125I-acetylated LDL, as well as a dose-dependent inhibition of 125I-acetylated LDL binding to these cells. Scatchard analysis of binding curves indicated that the diminished binding was due to a decrease in the number of scavenger receptor molecules at the cell surface rather than to a change in the affinity of the receptors for their ligand. Since castanospermine-treated cells had the same total number of cellular receptor molecules as did control cells, it seemed likely that castanospermine caused an alteration in receptor targeting, rather than an inhibition in receptor synthesis or a stimulation in receptor degradation. Density gradient fractionation of cell homogenates showed that castanosperminetreated cells did have a much greater percentage of scavenger LDL receptor molecules in the endoplasmic reticulum-Golgi fraction and fewer receptors in the plasma membrane fraction, whereas normal cells showed the opposite distribution.

Original languageEnglish (US)
Pages (from-to)8888-8895
Number of pages8
JournalBiochemistry
Volume32
Issue number34
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry

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