Stimulation of receptor‐mediated low density lipoprotein endocytosis in neuraminidase‐treated cultured bovine aortic endothelial cells

Eugene A. Sprague, Marianne Moser, Ellen H. Edwards, Colin J. Schwartz

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Sialic acids, occupying a terminal position in cell surface glycoconjugates, are major contributors to the net negative charge of the vascular endothelial cell surface. As integral membrane glycoproteins, LDL receptors also bear terminal sialic acid residues. Pretreatment of near‐confluent, cultured bovine aortic endothelial cells (BAEC) with neuraminidase (50 mU/ml, 30 min, 37°C) stimulated a significant increase in receptor‐mediated 125l‐LDL internalization and degradation relative to PBS‐treated control cells. Binding studies at 4°C revealed an increased affinity of LDL receptor sites on neuraminidase‐treated cells compared to control BAEC (6.9 vs. 16.2 nM/106 BAEC) without a change in receptor site number. This enhanced LDL endocytosis in neuraminidase‐treated cells was dependent upon the enzymatic activity of the neuraminidase and the removal of sialic acid from the cell surface. Furthermore, enhanced endocytosis due to enzymatic alteration of the 125l‐LDL molecules was excluded. In contrast to BAEC, neuraminidase pretreatment of LDL receptor‐upregulated cultured normal human fibroblasts resulted in an inhibition of 125l‐LDL binding, internalization, and degradation. Specifically, a significant inhibition in 125l‐LDL internalization was observed at 1 hr after neuraminidase treatment, which was associated with a decrease in the number of cell surface LDL receptor sites. Like BAEC, neuraminidase pretreatment of human umbilical vein endothelial cells resulted in enhanced receptor‐mediated 125l‐LDL endocytosis. These results indicate that sialic acid associated with either adjacent endothelial cell surface molecules or the endothelial LDL receptor itself may modulate LDL receptor‐mediated endocytosis and suggest that this regulatory mechanism may be of particular importance to endothelial cells.

Original languageEnglish (US)
Pages (from-to)251-262
Number of pages12
JournalJournal of Cellular Physiology
Volume137
Issue number2
DOIs
StatePublished - Nov 1988

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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