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Influence of Gangliosides on the IL-2– and IL-4–Dependent Cell Proliferation

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Abstract

Ganglioside-induced apoptosis in the cells of IL-2–dependent cytotoxic murine cell line CTLL-2 was shown to be caspase dependent: GM1-, GM2-, and GD3-induced suppression of cell proliferation was cancelled by a general caspase inhibitor Z-VAD-FMK. Ganglioside-induced apoptosis pathways are different for different individual glycolipids; the differences exist both at the initiation and effector stages of the caspase cascade. Only for GM1-induced process, molecular mechanisms of signal transduction coincide with the ones for CD95 and TNFα: the participation of both the main initiation caspases 8, 1, and 4, and caspases 3 and 9 as well, has been shown. Caspase 3 participates in the pathway induced by GM3, GD1a, GD1b, and GT1b, but not by GM2. As morphological features show, tumor-associated ganglioside GM2 is also a stimulus of programmed cell death (PCD) for CTLL-2 cell line: addition of GM2 into cell culture has resulted in appearance of annexin V-positive cells and in accumulation of DNA breaks (shown by the TUNEL direct dyeing of the open ends). But a caspase 3 inhibitor Z-DEVD-FMK did not restore the cell proliferation suppressed by GM2, and addition of a fluorescent substrate of caspase 3 Ac-DEVD-AFC did not result in the fluorescence development. So caspase 3 does not participate in downstream pathways of GM2-induced cell apoptosis, and a PCD-effector system other than the apoptosome-mediated one is involved here.

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Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

    Irina M. Molotkovskaya, Roman V. Kholodenko & Julian G. Molotkovsky

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  1. Irina M. Molotkovskaya
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  2. Roman V. Kholodenko
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  3. Julian G. Molotkovsky
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Molotkovskaya, I.M., Kholodenko, R.V. & Molotkovsky, J.G. Influence of Gangliosides on the IL-2– and IL-4–Dependent Cell Proliferation. Neurochem Res 27, 761–770 (2002). https://doi.org/10.1023/A:1020248722282

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