title: Oxidized low density lipoprotein stimulates aortic smooth muscle cell proliferation.
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.
authors.affiliation: Lipid Research Atherosclerosis Unit, Johns Hopkins University, School of Medicine, Baltimore, MD 21287-3654, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.forename: N
authors.initials: N
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism; D007700:Kinetics; D007790:Lactosylceramides / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature; D013936:Thymidine / Q000378:metabolism
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D007790:Lactosylceramides; D008077:Lipoproteins, LDL; D009025:Morpholines; C099252:oxidized low density lipoprotein; D012694:Serine; C009744:CDw17 antigen; C033110:RV 538; D016695:Glycosyltransferases; D005700:Galactosyltransferases; C023235:glucosylceramide beta-1-4-galactosyltransferase; D006026:Glycoside Hydrolases; D013936:Thymidine; D005690:Galactose