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  • Title: Oxidized low density lipoprotein stimulates aortic smooth muscle cell proliferation.
    Author: Chatterjee S, Ghosh N.
    Journal: Glycobiology; 1996 Apr; 6(3):303-11. PubMed ID: 8724138.
    Abstract:
    We have investigated the effects of oxidized low density lipoproteins (Ox-LDL) on aortic smooth muscle cell (SMC) proliferation and the biosynthesis of glycosphingolipids. We found that Ox-LDL exerted a concentration, time, and temperature dependent alteration of cell proliferation and the biosynthesis of lactosylceramide. At low concentrations (5-10 micrograms/ml medium) Ox-LDL stimulated cell proliferation measured by an increase in the incorporation of [3H]-thymidine in cells and the synthesis of lactosylceramide, but not glucosylceramide synthesis. Oxidized LDL exerted a threefold increase in the incorporation of [3H]-galactose and [3H]-serine in lactosylceramide. The activity of lactosylceramide synthetase; UDP-galactose glucosylceramide beta 1 --> 4 galactosyltransferase (GalT-2), but not glucosylceramide synthetase (GlcT-1) was stimulated by Ox-LDL. On the other hand, LDL suppressed the activity of GalT-2 in these cells. When cells were preincubated with antibody against Ox-LDL or GalT-2 it compromised the Ox-LDL mediated stimulated in cell proliferation and GalT-2 activity. Similarly, D-PDMP an inhibitor of GalT-2 compromised the Ox-LDL mediated effects in cells. In contrast, L-PDMP further stimulated the Ox-LDL mediated cell proliferation and GalT-2 activity. However, preincubation of cells with preimmune rabbit serum IgG failed to abrogate Ox-LDL mediated stimulation in cell proliferation and GalT-2 activity. In sum, we found that Ox-LDL stimulated aortic smooth muscle cell proliferation in culture. This effect resulted from Ox-LDL mediated activation of GalT-2 that produced lactosylceramide. Lactosylceramide in turn, contributed to cell proliferation. Such correlations are supportive of the notion that GalT-2 action mediates the signal transduction of Ox-LDL contributing to cell proliferation.
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