Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells

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 pap...

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Bibliographic Details
Published in:Neurochemical research 2006-10, Vol.31 (10), p.1171-1180
Main Authors: Omran, O M, Saqr, H E, Yates, Allan J
Format: Article
Language:English
Subjects:
Apoptosis - physiology
Blotting, Western
Brain Neoplasms - pathology
Caspase 8 - metabolism
Cell Line, Tumor
Gangliosides - physiology
Glioma - pathology
Humans
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Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-006-9147-2