Lactosylceramide stimulates aortic smooth muscle cell proliferation.
We have investigated the effects of various sphingolipids on aortic smooth muscle cell proliferation employing viable cell counting, [3H] thymidine incorporation into DNA and the release of lactate dehydrogenase. Assays for UDP Gal: GlcCer Bl-4 galactosyltransferase (GalT-2) in control and treated cells were pursued simultaneously. Lactosylceramide stimulated cell proliferation in the order of 5 fold. Antibody against LacCer but not GbOse3Cer blocked the proliferative effects of LacCer in these cells. This phenomena was specific for aortic smooth muscle cells as LacCer decreased cell viability of aortic endothelial cells and had no effect on pulmonary endothelial cells. D-PDMP inhibited the activity of GalT-2 in smooth muscle cells and markedly prevented cell proliferation. In contrast, L-PDMP stimulated the activity of GalT-2 in smooth muscle cells and stimulated cell proliferation. Antibody against GalT-2 inhibited cell proliferation. Our findings suggest that the activation of GalT-2 leads to increased LacCer levels, which in turn, may be involved in aortic smooth muscle cell proliferation.
Chatterjee
S
S
Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland 21205.
D000818:Animals; D015703:Antigens, CD; D001011:Aorta; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051147:Ganglioside Galactosyltransferase; D006028:Glycosphingolipids / Q000008:administration & dosage / Q000494:pharmacology*; D007790:Lactosylceramides; D008168:Lung / Q000166:cytology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011817:Rabbits; D013107:Sphingolipids / Q000494:pharmacology; D013997:Time Factors
D015703:Antigens, CD; D006028:Glycosphingolipids; D007790:Lactosylceramides; D009025:Morpholines; D013107:Sphingolipids; C009744:CDw17 antigen; C033110:RV 538; D005700:Galactosyltransferases; D051147:Ganglioside Galactosyltransferase