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

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 degrees C) stimulated a significant increase in receptor-mediated 125I-LDL internalization and degradation relative to PBS-treated control cells. Binding studies at 4 degrees C revealed an increased affinity of LDL receptor sites on neuraminidase-treated cells compared to control BAEC (6.9 vs. 16.2 nM/10(6) 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 125I-LDL molecules was excluded. In contrast to BAEC, neuraminidase pretreatment of LDL receptor-upregulated cultured normal human fibroblasts resulted in an inhibition of 125I-LDL binding, internalization, and degradation. Specifically, a significant inhibition in 125I-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 125I-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.

Enhanced expression of granulosa cell low density lipoprotein receptor activity in response to in vitro culture conditions

“…Thus, if a new LDL receptor protein is not being synthesized in granulosa cells during the 96-h experimental period in culture, and yet receptor function is clearly increased, what cellular mechanisms may be involved? For one, existing LDL receptors could be functionally unmasked; this could be due to increased synthesis (or functioning) of a receptor-activating factor, or the release of an inhibitory factor which controls LDL receptor function in steroidogenic tissues, or an alteration in receptor aggregation or configuration (Sprague et al, 1988;Chappell et al, 1991;Li et al, 1991;Pate1 et al, 1993). Or, as has been demonstrated in other systems (Czech et al, 19901, various intracellular signals (Bihain et al, 1989;Rouis et al, 1984;Liu et al, 1993) could alter receptor distribution and recycling kinetics in the cells, and translocation of the LDL receptor to the cell surface could be altered as time in culture increases.…”

Possible Interactions between Antioxidant Enzymes and Free Sialic Acids in Saliva: A Preliminary Study on Elite Judoists

“…ponents of cell membrane such as nucleic acids, proteins, and polyunsaturated fatty acids (PUFA) [9,10]. On the other hand, sialic acids (Sias) are important components of cell membrane to provide cell-to-cell interactions [20,21]. Some evidences confirm the relationship between Sias and diseases such as cardiovascular diseases and some cancer formations [15,19,23].…”

Sialidase down-regulation reduces non-HDL cholesterol, inhibits leukocyte transmigration, and attenuates atherosclerosis in ApoE knockout mice

“…Desialylation of ApoB increases the clearance of LDL 4 (17,18). The LDL receptor (LDLR) is also sialylated (19)…”