RESUMO
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.