title: Oxidized low density lipoproteins and lactosylceramide both stimulate the expression of proliferating cell nuclear antigen and the proliferation of aortic smooth muscle cells.
abstract: We have previously shown that oxidized low density lipoproteins (Ox-LDL) at low concentrations (10 micrograms/ml) via activating a UDP-galactose: glucosylceramide, beta 1-->4 galactosyl-transferase (GalT-2) and producing lactosylceramide can stimulate the proliferation of aortic smooth muscle cells. In this report, we present evidence that Ox-LDL and LacCer, both can induce the expression of proliferating cell nuclear antigen (cyclin). Ox-LDL and LacCer both exerted a time-dependent stimulation of cyclin expression. Maximum increase (3-fold) in cyclin expression occurred between 30-120 min after Ox-LDL/LacCer addition and decreased thereafter. D-threo-l-phenyldecanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of GalT-2, inhibited cell proliferation as well as cyclin expression. This inhibitor also abrogated the Ox-LDL mediated expression of proliferating cell nuclear antigen (cyclin). In contrast, the L-enantiomer of PDMP (L-PDMP) stimulated the expression of cyclin and augmented the Ox-LDL mediated expression of cyclin in these cells. Maximum increase in the expression of cyclin occurred with 20 mumole of L-PDMP and 10 micrograms of Ox-LDL. This overall pattern of Ox-LDL and LacCer mediated regulation is similar to that of the c-fos protooncogenes reported previously by us. We hypothesize that the early induction of GalT-2 may serve as an "Immediate early gene" that plays a role in the signalling cascade by LacCer and involves the kinase c-fos induction and subsequent expression of cyclins. Thus, GalT-2 may play a role in the proliferative response in aortic smooth muscle cells by Ox-LDL.
authors.affiliation: Dept. of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287-3654, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D015703:Antigens, CD; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007790:Lactosylceramides / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011817:Rabbits
chemical_list: D015703:Antigens, CD; D004791:Enzyme Inhibitors; D007790:Lactosylceramides; D008077:Lipoproteins, LDL; D009025:Morpholines; D018809:Proliferating Cell Nuclear Antigen; C099252:oxidized low density lipoprotein; C009744:CDw17 antigen; C033110:RV 538; D005700:Galactosyltransferases