Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells

Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells
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DOI:
10.1006/cyto.1997.0252
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发表时间:
1997-11-01
期刊:
影响因子:
3.8
通讯作者:
Fiers, W
Fiers, W
中科院分区:
医学3区
文献类型:
--
作者:
Vercammen, D;Vandenabeele, P;Fiers, W

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将人PAS基因导入小鼠纤维肉瘤L929细胞。分析肿瘤坏死因子(TNF)或PAS激动型抗体处理后的细胞死亡模式。当启动肿瘤坏死因子受体时,PAS抗原聚集会导致细胞死亡。N-对甲苯磺酰基-L-苯丙氨酸氯甲基酮和N-α-对甲苯磺酰基-L-赖氨酸氯甲基酮对肿瘤坏死因子诱导的细胞杀伤有保护作用,而PAS介导的细胞死亡作用较强。氯化锂对肿瘤坏死因子的细胞毒性有协同作用,但不影响PAS介导的死亡,而星形孢子素对这两种类型的细胞死亡都有促进作用。DNA合成抑制剂Aphidicolin和羟基脲可使细胞对PAS诱导的杀伤反应敏感,但对肿瘤坏死因子的细胞毒作用无明显影响。最后,我们证明了增加放线菌素D或放线菌亚胺的浓度对两种类型的细胞杀伤的影响是非常不同的。我们得出的结论是,根据触发因素,同一种细胞类型可以发生坏死或凋亡,尽管这两种途径可能共享一些细胞成分,但两种类型的细胞死亡的信号转导是不同的。(C)1997年学术出版社有限公司。
Murine fibrosarcoma L929 cells were transfected with human Pas cDNA. The mode of cell death was analysed following treatment either with tumour necrosis factor (TNF) or with agonistic antibodies to Pas. While triggering of the TNF receptors led to necrosis, clustering of the Pas antigen resulted in apoptotic cell death. N-tosyl-L-phenylalanine chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl ketone, two serine protease inhibitors, had a protective effect on TNF-induced killing, while Pas-mediated cell death was rather enhanced. Lithium chloride, which had a synergistic effect on TNF cytotoxicity, did not affect Pas-mediated death, whereas staurosporine had an enhancing effect on both types of cell death. Aphidicolin and hydroxyurea, inhibitors of DNA synthesis, were able to sensitize cells to Pas-induced killing, but had no effect on TNF cytotoxicity. Finally, we demonstrate that the effect of increasing concentrations of actinomycin D or cycloheximide is very different for the two types of cell killing. We conclude that either necrosis or apoptosis can occur in the same cell type, depending on the trigger, and that, although both pathways perhaps may share some cellular components, signal transduction is different for the two types of cell death. (C) 1997 Academic Press Limited.