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Studies on the significance of bioactive gangliosides in cellular growth and differntiation.

生物活性神经节苷脂在细胞生长和分化中的意义的研究。

基本信息

批准号：
60440102
负责人：
NAGAI Yoshitaka
金额：
$ 15.49万
依托单位：
Faculty of Medicine, Unversity of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1988
项目状态：
已结题

项目摘要

Carbohydrate recognition at cell surface is known to importantly be involved in cell to cell interactions, cell growth and differentiation.Most of such modulatory potentials have so far been reported on a family of sialylated glycosphingolipids, gangliosides, using cultured cell system added with these glycolipids exogenously. We previously reported that a disialoganglioside GD3 strongly promotes ions and water transport in cultured kidney epithelial cells (MDCK). Newly and specific appearance of GD3 was observed in rat embryonic fibroblastic cells, 3Y1, which were transfected and transformed with various oncogenes of DNA-virus origin (adenovirus E1A, SV40-T and myc). The monoclonal antibody to GD3 reversibly inhibits cell growth of these cells. The remarkable elevation of GD3 was reported on neuron and glial cells in their proliferative states. More recently we have found that a tetrasialoganglioside G 1b specifically can promote differentiation of the human neuroblastoma cells, leading to the promotion of neuritogenesis and also that G 1b specifically stimulates the phosphorylation of several cell surface proteins of the same cells, when the G 1b and ATP are added to the cells. The results indicate that this cell surface protein phosphorylation might be carried out by unique cell surface membrane protein kinase(s) (ecto-Gg kinase) which is specifically activated by a particular ganglioside. Inhibition of this phosphorylation resulted in the inhibition of G 1b-dependent promotion of neuritogenesis, strongly suggesting the interrelationship between those two cell events and occurrence of a new biosignal transduction, ecto biosignal transduction system.

糖分子在细胞表面的识别与细胞间的相互作用、细胞的生长和分化密切相关，目前已报道的糖分子识别调控机制主要是通过在细胞培养体系中外源性添加糖脂类化合物神经节苷脂来实现的。我们以前报道过，一个disialoganglioside GD 3强烈促进离子和水的运输在培养的肾上皮细胞（MDCK）。在大鼠胚胎成纤维细胞3 Y1中观察到GD 3的新的和特异性的出现，该细胞用DNA病毒来源的各种癌基因（腺病毒E1 A、SV 40-T和myc）转染并转化。GD 3的单克隆抗体可逆地抑制这些细胞的细胞生长。GD 3的显着升高的神经元和神经胶质细胞在其增殖状态。最近，我们发现四唾液酸神经节苷脂G1 b可以特异性地促进人神经母细胞瘤细胞的分化，从而促进神经突的发生，并且当G1 b和ATP被添加到细胞中时，G1 b还特异性地刺激相同细胞的几种细胞表面蛋白的磷酸化。结果表明，这种细胞表面蛋白磷酸化可能是由独特的细胞表面膜蛋白激酶（外-Gg激酶）进行的，该激酶被特定的神经节苷脂特异性激活。这种磷酸化的抑制导致抑制G1 b依赖的促进轴突发生，强烈表明这两个细胞事件之间的相互关系和发生一个新的生物信号转导，外生物信号转导系统。