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 [3H]PDBu binding approximately 2-3 fold. This response was inhibited by preincubating the cells with an inhibitor of phospholipase C (PLC), U73122, suggesting that PLC mediates the induction of PKC translocation by PDGF. PDGF also increased the concentration of [Ca2+]i that was attenuated in a calcium-free medium. This indicates that PDGF-induced elevation of [Ca2+]i is mainly due to influx of extracellular calcium. PDGF-stimulated translocation of PKC was inhibited by the intracellular calcium buffer BAPTA/AM. All gangliosides studied except GM3 inhibited these responses with similar efficacy. Collectively, these results indicate that the signal transduction pathway initiated by PDGF leading to PKC translocation in U-1242 MG cells is intact, and this pathway is inhibited by several gangliosides.
Saqr
H E
HE
Department of Pathology, Ohio State University, Columbus 43210, USA.
Walters
J D
JD
Guan
Z
Z
Stokes
B T
BT
Yates
A J
AJ
D002118:Calcium / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D005732:Gangliosides; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D002118:Calcium