Rodríguez René, Campa Victor M, Riera José, Carcedo M Teresa, Ucker David S, Ramos Sofía, Lazo Pedro S
Instituto Universitario de Oncología del Principado de Asturias and Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33071 Oviedo, Spain.
Eur Cytokine Netw. 2007 Dec;18(4):172-80. doi: 10.1684/ecn.2007.0106. Epub 2007 Nov 12.
Tumor necrosis factor (TNF) is known to be a mediator of a variety of cellular responses including apoptotic death or proliferation depending on the target cell and the environmental conditions. We show here that TNF triggers both growth and death signals in NIH 3T3 murine fibroblasts. In cells arrested in G(0) by serum deprivation, TNF drives approximately 50% of them to enter the cell cycle, but kills the cells that remain quiescent. The presence of serum prevents toxic effects of TNF, suggesting that TNF can cooperate to drive cells through the cell cycle, but is unable to do so by itself and alternatively it triggers death signals in cells unable to proliferate. Interestingly, TNF induces a similar toxic effect in cells forced to stay at the G(1)/S border, S or M phases. We have explored the TNF apoptotic pathway in arrested cells. This mechanism is not due to the loss of the anti-apoptotic capacity of NFkappaB and is mediated by mitochondria since Bcl-2 overexpression partially inhibits cell death. There are, however, interesting differences in the kinetics of mitochondrial events which indicate that this form of sensitization to TNF leads to an apoptotic mechanism different from that observed after sensitization by RNA synthesis inhibition.
肿瘤坏死因子（TNF）是多种细胞反应的介质，根据靶细胞和环境条件，这些反应包括凋亡性死亡或增殖。我们在此表明，TNF在NIH 3T3小鼠成纤维细胞中触发生长和死亡信号。在因血清剥夺而停滞于G(0)期的细胞中，TNF促使约50%的细胞进入细胞周期，但会杀死仍处于静止状态的细胞。血清的存在可防止TNF的毒性作用，这表明TNF可协同驱动细胞通过细胞周期，但自身无法做到这一点，相反，它会在无法增殖的细胞中触发死亡信号。有趣的是，TNF在被迫停留在G(1)/S边界、S期或M期的细胞中诱导类似的毒性作用。我们在停滞的细胞中探索了TNF凋亡途径。这种机制并非由于NFκB抗凋亡能力的丧失，而是由线粒体介导的，因为Bcl-2的过表达部分抑制细胞死亡。然而，线粒体事件的动力学存在有趣的差异，这表明这种对TNF的致敏形式导致的凋亡机制不同于RNA合成抑制致敏后观察到的凋亡机制。
