GANGLIOSIDES INHIBIT PDGF-INDUCED SIGNAL-TRANSDUCTION EVENTS IN U-1242 MG HUMAN GLIOMA-CELLS

In this study we investigated the responses of intracellular calcium ( [Ca2+](i)) and protein kinase C (PKC) to PDGF in U-1242 MG cells. PDGF -BB stimulated [H-3]PDBu binding approximately 2-3 fold. This response was inhibited by preincubating the cells with an inhibitor of phospho lipase C (PLC), U73122, suggesting that PLC mediates the induction of PKC translocation by PDGF. PDGF also increased the concentration of [C a2+](i) that was attenuated in a calcium-free medium, This indicates t hat PDGF-induced elevation of [Ca2+](i) is mainly due to influx of ext racellular calcium. PDGF-stimulated translocation of PKC was inhibited by the intracellular calcium buffer BAPTA/AM. All gangliosides studie d except GM3 inhibited these responses with similar efficacy. Collecti vely, these results indicate that the signal transduction pathway init iated by PDGF leading to PKC translocation in U-1242 MG cells is intac t, and this pathway is inhibited by several gangliosides.