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肿瘤坏死因子α(tumor necrosis factor alpha,TNFα)诱导的L929细胞死亡是研究细胞程序性坏死的重要模型,但也有报道称,TNFα处理后的L929细胞发生了凋亡。该研究以所在实验室保存的L929细胞(L929-A)和从商业化细胞库购买的L929细胞(L929-N)为模型,进一步鉴定了TNFα诱导的L929细胞死亡类型与调控机制。结果发现,TNFα处理后的L929-A细胞中出现了凋亡特征,且阻断胱冬肽酶(caspase)信号通路可显著抑制TNFα诱导的L929-A细胞死亡,但却促进TNFα诱导的L929-N细胞死亡。此外,受体相互作用蛋白1(receptor-interacting protein 1,RIP1)在TNFα诱导的两种L929细胞死亡过程中都具有关键性的调控作用,表明TNFα处理后的L929-A细胞发生了RIP1依赖的细胞凋亡,而L929-N细胞发生了程序性坏死(necroptosis)。同时,启动细胞程序性坏死的关键蛋白RIP3(receptor-interacting protein 3)在L929-N细胞中表达水平显著高于L929-A细胞,因此,RIP3的这种差异表达可能是决定两种L929细胞在TNFα处理后发生不同类型细胞程序性死亡的重要原因。
L929 cell death induced by tumor necrosis factor alpha (TNFα) is an important model for the study of programmed cell death. However, it has also been reported that L929 cells apoptosis after TNFα treatment. This study further identified the type and mechanism of TNFα-induced L929 cell death by using L929 cells (L929-A) and L929-N cells purchased from a commercial cell bank (L929-N) in their laboratories as a model. The results showed that the apoptotic characteristics of L929-A cells were observed in TNFα-treated L929-A cells. Blocking the caspase signaling pathway could significantly inhibit the TNFα-induced L929-A cell death but promoted the TNFα-induced L929- N cell death. In addition, receptor-interacting protein 1 (RIP1) plays a key regulatory role in the TNFα-induced apoptosis of both L929 cells, indicating that RIP1-dependent Apoptosis, whereas L929-N cells undergo necroptosis. Meanwhile, the expression of RIP3, a key protein that initiates apoptosis, was significantly higher in L929-N cells than in L929-A cells. Therefore, this differential expression of RIP3 may be the key factor that determines the expression of two kinds of L929 cells in TNFα treatment of different types of programmed cell death of the important reasons.