Wang Xiaoxu, Li Yiyang, Wang Yuliu, Liu Yanjun, Xue Changhu, Cong Peixu, Xu Jie
College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, People's Republic of China.
Laboratory of Marine Drugs and Biological Products, Pilot National Laboratory for Marine Science and Technology, Qingdao, Shandong, People's Republic of China.
Biosci Biotechnol Biochem. 2021 Feb 24;85(3):675-686. doi: 10.1093/bbb/zbaa088.
Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.
神经节苷脂（GLS）广泛分布于所有组织中，但在神经系统中高度富集。目前，尽管对内源性GLS的神经功能进行了广泛研究，但尚不清楚外源性GLS如何调节神经突生长。在此，我们在体外评估了海胆神经节苷脂（SU-GLS）的神经突生长活性及其机制。这些不同糖基化的SU-GLS，包括GM4(1S)、GD4(1S)、GD4(2A)和GD4(2G)，以剂量依赖性和结构选择性方式促进了NGF诱导的PC12细胞的分化。硫酸酯型和双唾液酸型GLS比单唾液酸神经节苷脂GM1表现出更强的神经突生长作用。此外，SU-GLS可能通过靶向酪氨酸激酶受体（TrkA和TrkB）并激活MEK1/2-ERK1/2-CREB和PI3K-Akt-CREB途径，作为具有神经突生长作用的神经营养因子发挥作用。这种激活导致脑源性神经营养因子（BDNF）和神经生长因子（NGF）的表达和分泌增加。这些途径通过特异性抑制剂得到了验证。我们的结果证实了SU-GLS在体外的神经突生长功能，并表明它们作为神经突生长天然营养物质的潜在作用。
