Koike T, Fehsel K, Zielasek J, Kolb H, Burkart V
Diabetes Research Institute, University of Düsseldorf, Germany.
Immunol Lett. 1993 Mar;35(3):207-12. doi: 10.1016/0165-2478(93)90184-4.
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.
分析了神经节苷脂对肿瘤坏死因子α介导的细胞毒性的调节作用。当TNFα敏感的纤维肉瘤细胞系L929的细胞与重组TNFα（156或312 pg/ml）孵育16小时时，它们分别被裂解至65.2%或78.0%。牛脑神经节苷脂混合物（BBG，Cronassial）的存在以剂量依赖性方式抑制TNFα介导的裂解（IC50约为1 mg/ml）。用2 mg/ml BBG可实现最大抑制（对于156 pg/ml TNFα抑制82.6%，对于312 pg/ml TNFα抑制88.5%）。原位缺口平移显示，BBG（2 mg/ml）可将TNFα诱导的DNA链断裂细胞数量从71.2%显著降低至6.6%（P < 0.0001），表明对TNFα介导的凋亡具有保护作用。我们得出结论，BBG可防止TNFα对肿瘤细胞的细胞毒性作用。这种抑制作用可能是由于神经节苷脂干扰细胞内信号转导途径，导致DNA裂解核酸内切酶的激活受到抑制。
