Effects of SDF-1α and gp120IIIB on apoptotic pathways in SK-N-SH neuroblastoma cells

SDF-1α (10 nM) and gp120IIIB (2 nM) induced similar levels of apoptosis after 24 h of incubation (49 ± 4% and 48 ± 3%, respectively, of the neurons were apoptotic). SDF1α-induced apoptosis was completely abolished by the inhibition of Src phosphorylation by PP2. Exposure to SDF-1α (10 nM) triggered an increase in Src phosphorylation, with a maximum after 20 min of incubation (1.80 ± 0.24 times higher than control, P = 0.01). NMDA calcium flux was enhanced only if cells were incubated with SDF-1α for 20 min before applying NMDA. By contrast, gp120IIIB-induced apoptosis was not affected by the inhibition of Src phosphorylation. Moreover, gp120IIIB enhanced NMDA calcium flux immediately, without modifying Src phosphorylation status. Finally, levels of phospho-JNK increased following exposure to gp120IIIB (by a factor of 1.46 ± 0.4 at 120 min, P = 0.03), but not after exposure to SDF-1α. Thus, SDF-1α and gp120IIIB induced a similar level of neuronal apoptosis, but by activating different intracellular pathways. SDF-1α enhanced NMDA activity indirectly via Src phosphorylation, whereas gp120IIIB probably activated the NMDA receptor directly and phosphorylated JNK.