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The biological significance and role of GD3 ganglioside in U-1242MG glioma cells

Omran, Ola Mahmoud F.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1086098340

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Pathology.
Human glioblastoma multiforme (GBM) is the most common malignant glioma in adults. GBM constitutes a major problem in clinical management due to its high infiltrative ability, resistance to the current cancer therapy that account for its bad prognosis. Specific target molecules produced in the cells are required to control the biology of malignant glioma cells and facilitate the treatment strategies. Many reports demonstrated that exogenous addition of the disialoganglioside GD3 induces apoptosis in various cell types, acting mainly through the mitochondrion. The overall aim of this work is to elucidate the biological roles of endogenously synthesized GD3 on U-1242MG glioblastoma cell line. We conducted experiments to elucidate the biological effects of endogenous GD3 expression on U-1242MG cells, and the results of these showed that the expression of GD3 was associated with apoptosis. After establishing that GD3 causes apoptosis, we investigated some of the mechanisms leading to apoptosis that are induced by three death ligands (FasL, TNF-α and TRAIL). We found that of the three death ligands only TRAIL-induced apoptosis in U-1242MG cells. We also found that three death receptors (DR5, Fas and TNF-R1) involved in the early stage of apoptosis are located in the caveolin-1 enriched fractions. Furthermore, TRAIL initiates the subcellular relocalization of several death receptors and other apoptotic molecules. We found that endogenously expressed GD3 is localized in the caveolae of U42-GRD2 cells, and that GD3 expression induced translocation of the death receptors Fas, TNF-R1, DR5 and other apoptotic molecules such as caspase-8 into the caveolae as a part of the molecular mechanism of GD3-induced apoptosis. Moreover, in contrast to caspase-8, the subcellular localization of cytochrome c was not affected by endogenous GD3 expression indicating that the mitochondrial pathway leading to apoptosis was probably not involved. From the above we conclude that the endogenous expression of GD3 induces apoptosis in U-1242MG glioma cells mediated through the extrinsic, not the intrinsic pathway.
Allan Yates (Advisor)
Hany Saqr (Other)
James Waldman (Other)
James Van Brocklyn (Other)
134 p.
Health Sciences, Pathology
GD3 ganglioside; Gliomas; Apoptosis; Caspase-8; DR5

Recommended Citations

Citations

  • Omran, O. M. F. (2004). The biological significance and role of GD3 ganglioside in U-1242MG glioma cells [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1086098340

    APA Style (7th edition)

  • Omran, Ola. The biological significance and role of GD3 ganglioside in U-1242MG glioma cells. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1086098340.

    MLA Style (8th edition)

  • Omran, Ola. "The biological significance and role of GD3 ganglioside in U-1242MG glioma cells." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1086098340

    Chicago Manual of Style (17th edition)

osu1086098340
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© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.