Interaction of GM1 ganglioside with PC12 pheochromocytoma cells: serum- and NGF-dependent effects on neuritic growth (and proliferation).

The effects of ganglioside GM1 on proliferation and neuritic growth of PC12 pheochromocytoma cells were studied in the presence and absence of nerve growth factor (NGF). In the absence of NGF, but not in its presence, a decrease in the total number of PC12 cells was first observed after 4-6 days of culture with 10(-6) M GM1 in 0.1% fetal calf serum, and with 10(-3) M GM1 on 10% serum. NGF, with or without GM1, limits cell growth to the first 4-6 days. GM1 enhanced neuritic recruitment with serum concentrations of 0.3% or more. Optimal neurite response varied from 10(-6) M GM1 with 0.3% serum to 10(-4) M GM1 with 10% serum. The influence of GM1 on neurites became more pronounced with increasing serum concentrations, becoming maximal with 1% or greater serum. Serum exhibited a concentration-dependent inhibitory influence (lag) on NGF-induced neuritic recruitment, which was abolished by GM1. Rates of neuritic recruitment following the lag were unaffected by GM1, while showing an inverse correlation with serum concentrations of 0.1-0.5%. Serum may delay the NGF-induced neuritic recruitment of PC12 cells by two independent mechanisms. These results suggest that GM1, in some manner, prevents the serum-induced delay in the onset of neuritic recruitment, rather than stimulating the rate at which it precedes.