神经节苷脂GM_1和GM_3对受体介导的转铁蛋白内吞过程的影响

THE EFFECT OF GANGLIOSIDE GM_1 AND GM_3 ON RECEPTOR-MEDIATED ENDOCYTOSIS OF TRANSFERRIN

我们从正常人脑及肝脏中分离得到纯化的神经节苷脂GM_1[Gal-GalNAc-(NeuNAc)Gal-Glc-Cer]和GM_3[NeuNAc-Gal-Glc-Cer],发现外源性GM_1或GM_3的加入能不同程度地抑制SMMC-7721人肝癌细胞的生长,但仅GM_3能抑制转铁蛋白(Tf)促进的细胞生长。进一步的研究发现,GM_3并不影响Tf与细胞膜表面受体的结合,而是抑制了受体介导的Tf内吞过程,内吞囊泡的形成及融合均受到影响。结果提示:GM_3在膜中的嵌入,可能使受体的构象发生变化或影响了膜的流动性,从而抑制Tf的内吞过程。

Pure ganglioside GM1 and GM3 were isolated from human brain and liver tissues. It was discovered that exogenously added GM1 or GM3 inhibited the growth of SMMC-7721 human hepatocellular carcinoma cells to different extents. Only-GM3-fed cells became refractory to growth stimulation by transferrin in chemically defined media. Further studies indicated that GM3 had no effect on the binding of transferrin to its receptor on the surface of SMMC-7721 cells, but it inhibited receptor-mediated endocytosis of transferrin. The formation of vesicles and fusion between the endocytic vesicles were both influenced. It was suggested that the incorporation of GM3 in cell membranes may change the structure of the receptor or the fluidity of the membrane and then influence the endocytosis of transferrin.