Hynds D L, Burry R W, Yates A J
Department of Pathology, Ohio State University, Columbus, USA.
J Neurosci Res. 1997 Mar 15;47(6):617-25. doi: 10.1002/(sici)1097-4547(19970315)47:6<617::aid-jnr7>3.0.co;2-g.
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 microM GM1, and percent of neurite-bearing cells being below controls with 25, 50, and 100 microM 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.
已知外源性添加的神经节苷脂可促进多种细胞类型的神经突生长，包括一些神经母细胞瘤细胞系。为了研究SH-SY5Y人神经母细胞瘤中的神经突发生，我们使细胞血清饥饿24小时，然后将它们暴露于神经节苷脂（GM1、GM3或GT1b）、血小板衍生生长因子（PDGF）、胰岛素、神经生长因子（NGF）、胰岛素样生长因子I（IGF-I）或这些物质的组合中3天。我们使用图像分析测量了神经突生长的四个参数。PDGF诱导SH-SY5Y细胞的神经突生长，而GM1则抑制这种生长。这两种现象均呈剂量依赖性，当GM1浓度为100 microM时，神经突/细胞数和神经突长度低于对照组，当GM1浓度为25、50和100 microM时，有神经突的细胞百分比低于对照组。GM3和GT1b也得到了类似但更具抑制性的结果。胰岛素和IGF-I诱导的神经突发生反应比PDGF弱，并且也受到神经节苷脂的抑制。NGF对神经突生长没有影响，但即使在未用生长因子处理的细胞中，神经节苷脂仍然具有抑制作用。由此我们得出结论，神经节苷脂抑制SH-SY5Y细胞中自发的和营养因子诱导的神经突生长。对于GM1和GT1b，但不包括GM3，这可能涉及对营养因子受体功能的抑制。
