GANGLIOSIDES INHIBIT GROWTH FACTOR-STIMULATED NEURITE OUTGROWTH IN SH-SY5Y HUMAN NEUROBLASTOMA-CELLS

Exogenously added gangliosides are known to promote neurite outgrowth in a variety of cell types, including some neuroblastoma cell lines, T o study neuritogenesis in SH-SY5Y human neuroblastoma we serum starved the cells for 24 hr and exposed them to gangliosides (GM1, GM3, or GT 1b), platelet-derived growth factor (PDGF), insulin, nerve growth fact or (NGF), insulin-like growth factor I (IGF-I), or combinations of the se for 3 days, We measured four parameters of neurite outgrowth using image analysis, PDGF induced neurite outgrowth in SH-SY5Y and GM1 inhi bited this, Both phenomena were dose-dependent with neurites/cell and neurite length being below controls with 100 mu M GM1, and percent of neurite-bearing cells being below controls with 25, 50, and 100 mu M G M1, Similar but more inhibitory results were obtained with GM3 and GT1 b. Insulin and IGF-I induced a neuritogenic response that was less pot ent than that of PDGF and was also inhibited by gangliosides, NGF had no effect on neurite outgrowth but gangliosides were still inhibitory even in cells not treated with growth factors, From this we conclude t hat gangliosides inhibit spontaneous and trophic factor-induced neurit e outgrowth in SH-SY5Y cells, For GM1 and GT1b, hut not GM3, this prob ably involves inhibition of trophic factor receptor function. (C) 1997 Wiley-Liss, Inc.