Gangliosides inhibit growth factor-stimulated neurite outgrowth in SH-SY5Y human neuroblastoma cells

Abstract

Exogenously added gangliosides are known to promote neurite outgrowth in a variety of cell types, including some neuroblastoma cell lines. To study neuritogenesis in SH‐SY5Y human neuroblastoma we serum starved the cells for 24 hr and exposed them to gangliosides (GM1, GM3, or GT1b), platelet‐derived growth factor (PDGF), insulin, nerve growth factor (NGF), insulin‐like growth factor I (IGF‐I), or combinations of these for 3 days. We measured four parameters of neurite outgrowth using image analysis. PDGF induced neurite outgrowth in SH‐SY5Y and GM1 inhibited this. Both phenomena were dose‐dependent with neurites/cell and neurite length being below controls with 100 μM GM1, and percent of neurite‐bearing cells being below controls with 25, 50, and 100 μM GM1. Similar but more inhibitory results were obtained with GM3 and GT1b. Insulin and IGF‐I induced a neuritogenic response that was less potent 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 that gangliosides inhibit spontaneous and trophic factor‐induced neurite outgrowth in SH‐SY5Y cells. For GM1 and GT1b, but not GM3, this probably involves inhibition of trophic factor receptor function. J. Neurosci. Res. 47:617–625, 1997. © 1997 Wiley‐Liss, Inc.

Sialic acid residues on astrocytes regulate neuritogenesis by controlling the assembly of laminin matrices

“…These values are all below the limit of about 150 µm reported for laminin assembled on glass at acidic pH (Freire et al, 2002). Nevertheless, the observation that the average neurite size obtained in the presence of PC and GM1 (15-25 µm) is much lower than obtained in the absence of lipids suggests that lipids themselves, besides an effect on the orientation of laminin assembly, might also directly inhibit the growth of neurites (Hynds et al, 1997), thus contributing to an overall decrease in the sizes of neurites observed in the assay. Results presented in this section show that the presence of an artificial negative surface can modulate the morphology and the neuritogenic potential of laminin aggregates, thus mimicking the effect of negative groups on the membrane of astrocytes.…”

Platelet-derived Growth Factor-mediated Induction of the Synaptic Plasticity Gene Arc/Arg3.1

“…PDGF pretreatment is known to attenuate excitotoxic death in cultured hippocampal neurons (7) and induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions (41). Another proposed mechanism by which PDGF mediates its neuroprotective effect is through the induction of neurite outgrowth, as demonstrated in a variety of in vitro neuronal systems, including fetal rat and human dopaminergic neurons (39), SH-SY5Y cells (42), and hippocampal HiB5 cells (43). The possibility has been raised that PDGF might act as a neuromodulator in the central nervous system.…”

Rit promotes MEK-independent neurite branching in human neuroblastoma cells

“…In the present study, Rit increased neurite initiation (the number of neurites per cell and the percent of neurite-bearing cells), elongation (the total neurite length per cell) and arborization (the number of branch points per neurite) in SH-SY5Y human neuron-like cells on either endogenous matrix or purified laminin-1. Interestingly, Rit significantly increases neurite arborization, an atypical behavior for SH-SY5Y cells (Hynds et al, 1997;Hynds and Snow, 1999;Hynds and Snow, 2001). This suggests that Rit functions early in neuronal development to determine process identity (i.e.…”

“…These cells, originally subcloned from a metastatic neuroblastoma, represent a homogenous culture of sympathetic noradrenergic neurons (Ross et al, 1983) and emulate the behavior and biology of primary neurons (Ross et al, 1983;Påhlman et al, 1990;Leli et al, 1992;Påhlman et al, 1992;Choi et al, 1994;Leventhal and Feldman, 1995;Smith et al, 1995;Hynds et al, 1997;Hynds and Snow, 1999;Zeidman et al, 1999;Encinas et al, 2000;Hynds and Snow, 2001;Snow et al, 2001). Adenovirus-mediated expression of CA-Rit induced extensive neurite outgrowth and, importantly, branching in SH-SY5Y cells cultured on endogenous extracellular matrix or purified laminin-1.…”