Gangliosides protect from TNF alpha-induced apoptosis.
The modulation of tumor necrosis factor alpha-mediated cytotoxicity by gangliosides was analyzed. When cells of the TNF alpha-sensitive fibrosarcoma cell line L929 were incubated for 16 h with recombinant TNF alpha (156 or 312 pg/ml), they were lysed to 65.2% or 78.0%, respectively. The presence of a bovine brain ganglioside mixture (BBG, Cronassial) inhibited the TNF alpha-mediated lysis in a dose-dependent manner (IC50 approximately 1 mg/ml). Maximum inhibition was achieved with 2 mg/ml BBG (82.6% inhibition for 156 pg/ml TNF alpha and 88.5% inhibition for 312 pg/ml TNF alpha). In situ nick translation revealed that BBG (2 mg/ml) significantly reduces the number of cells with TNF alpha-induced DNA-strand breaks from 71.2% to 6.6% (P < 0.0001), indicating a protection against TNF alpha-mediated apoptosis. We conclude that BBG prevents the cytotoxic action of TNF alpha on tumor cells. The inhibitory effect may be due to an interference of gangliosides with intracellular signal transduction pathways, resulting in an inhibition of the activation of DNA-cleaving endonucleases.
Diabetes Research Institute, University of Düsseldorf, Germany.
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T
Koike
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Fehsel
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Zielasek
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Kolb
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Burkart
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D016923:Cell Death; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000494:pharmacology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D005732:Gangliosides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C037470:cronassial