Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells.
Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells.
复制标题
GD3 诱导 U-1242 MG 胶质瘤细胞凋亡的分子机制。
DOI：
10.1007/s11064-006-9147-2
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发表时间：
2006
影响因子：
4.4
通讯作者：
Yates,AllanJ
中科院分区：
文献类型：
--
作者：
Omran,OM;Saqr,HE;Yates,AllanJ
越来越多的证据表明，双胞脂苷GD3参与了许多细胞系的凋亡。我们之前的研究表明，内源性GD3表达可诱导转染GD3合成酶基因的U-1242 MG胶质瘤细胞（U1242MG-GD3细胞）凋亡。本文将进一步探讨gd3诱导该细胞系细胞凋亡的分子机制。我们发现内源性合成的GD3定位于该细胞系的小窝，在那里它促进死亡受体5 （DR5）、肿瘤坏死因子受体1 （TNF-R1）和Fas （Apo-1）定位于小窝。此外，caspase-8被转移到空泡部分并被劈裂；然后将裂解的蛋白质重新定位到高密度部分。然而，GD3对连接蛋白fas相关死亡结构域（FADD）的分布没有影响。我们得出结论，GD3在外源性凋亡途径的早期发挥调控分子的作用。
An increasing amount of evidence indicates that the disialoganglioside GD3 is involved in apoptosis in many cell lines. Our previous studies demonstrated that endogenous GD3 expression induced apoptosis in U-1242 MG glioma cells transfected with the GD3 synthase gene (U1242MG-GD3 cells). In this paper, we present further investigations on the molecular mechanisms of GD3-induced apoptosis in this cell line. We found that endogenously synthesized GD3 localizes to the caveolae of this cell line, where it promotes the localization of death receptor 5 (DR5), tumor necrosis factor receptor-1 (TNF-R1), and Fas (Apo-1) to the caveolae. In addition, caspase-8 was translocated to the caveolar fraction and cleaved; the cleaved proteins were then re-located into the high density fractions. However, GD3 had no effect on the distribution of the adapter protein Fas-associated death domain (FADD). We conclude that GD3 functions as a regulatory molecule early in the extrinsic apoptosis pathway.