Xie K, Huang S, Dong Z, Fidler I
UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HMB 173,1515 HOLCOMBE BLVD,HOUSTON,TX 77030.
Int J Oncol. 1993 Dec;3(6):1043-8. doi: 10.3892/ijo.3.6.1043.
The purpose of this study was to determine whether the synthesis of endogenous nitric oxide (NO) is involved in the apoptosis of murine L929 transformed fibroblasts. L929 parental cells and L929 cells selected for resistance to tumor necrosis factor (TNF-alpha) were incubated in vitro with various concentrations of TNF-alpha, interleukin-1, and lipopolysaccharide (LPS) in the presence or absence of mouse interferon-gamma (IFN-gamma). The combination of subthreshold concentrations of IFN-gamma with the cytokines or LPS produced significant cell death within 48 h incubation. This cell death was associated with the induction of high levels of NO. Both cell death and NO production were significantly inhibited by the addition of N(G)-methyl-L-arginine (NMA), a specific inhibitor of nitric oxide synthase. The synergistic cytotoxicity was associated with extensive internucleosomal DNA fragmentation. NMA also inhibited this process. These data demonstrate the involvement of endogenous NO in cytokine-induced apoptosis of transformed cells.
本研究的目的是确定内源性一氧化氮（NO）的合成是否参与小鼠L929转化成纤维细胞的凋亡。将L929亲代细胞和对肿瘤坏死因子（TNF-α）具有抗性的L929细胞在体外与不同浓度的TNF-α、白细胞介素-1和脂多糖（LPS）一起培养，同时存在或不存在小鼠干扰素-γ（IFN-γ）。亚阈值浓度的IFN-γ与细胞因子或LPS的组合在孵育48小时内产生了显著的细胞死亡。这种细胞死亡与高水平NO的诱导有关。添加一氧化氮合酶的特异性抑制剂N（G）-甲基-L-精氨酸（NMA）可显著抑制细胞死亡和NO产生。协同细胞毒性与广泛的核小体间DNA片段化有关。NMA也抑制了这一过程。这些数据表明内源性NO参与了细胞因子诱导的转化细胞凋亡。
