The c-Rel transcription factor can both induce and inhibit apoptosis in the same cells via the upregulation of MnSOD
The c-Rel transcription factor can both induce and inhibit apoptosis in the same cells via the upregulation of MnSOD
复制标题
DOI：
10.1038/sj.onc.1205536
复制
发表时间：
2002-06-27
期刊：
影响因子：
8
通讯作者：
Abbadie, C
中科院分区：
文献类型：
--
作者：
Bernard, D;Monte, D;Abbadie, C
Rel/NF-kappaB 转录因子参与多种生理过程，包括细胞凋亡的调节。这些因子在不同的细胞模型中显示出促凋亡或抗凋亡活性，但目前，人们对这些相反作用的机制知之甚少。在这项研究中，我们发现 Rel/NF-kappaB 家族转录活性成员 c-Rel 的组成型表达首先诱导对 TNFα 诱导的细胞凋亡的抵抗，然后增加 HeLa 细胞的自发凋亡水平。抗凋亡和促凋亡作用均随着 c-Rel 过表达水平的增加而增加。 c-Rel 对锰超氧化物歧化酶 (MnSOD) 的上调可以解释快速的抗凋亡作用和延迟的促凋亡作用。事实上，MnSOD 的酶活性是转化 H2O2 中有毒的 O-2(.-)。因此，一方面，它的诱导有助于细胞抵抗 TNFα 刺激时产生的 O-2 凋亡爆发，但另一方面，它会导致 H2O2 逐渐积累，最终导致细胞凋亡。这些结果表明，Rel/NF-kappaB 因子的抗凋亡作用和促凋亡作用不一定是替代性的，而是可以通过同一靶基因的上调在同一细胞中连续发生。
Rel/NF-kappaB transcription factors are involved in several physiological processes, including the regulation of apoptosis. These factors were shown to exhibit pro- or anti-apoptotic activities in different cellular models, but at present, the mechanisms underlying these opposite effects are poorly understood. In this study, we show that the constitutive expression of a transcriptionally active member of the Rel/NF-kappaB family, c-Rel, first induces a resistance against TNFalpha-induced apoptosis and later increases the level of spontaneous apoptosis of HeLa cells. Both the anti- and pro-apoptotic effects increase with the level of c-Rel overexpression. The up-regulation by c-Rel of the manganese superoxide dismutase (MnSOD) could explain both the rapid anti-apoptotic effect and the delayed pro-apoptotic one. Indeed, the enzymatic activity of MnSOD is to transform the toxic O-2(.-) in H2O2. Hence, on one hand, its induction helps cells to resist against the apoptogenic burst of O-2 produced upon TNFalpha stimulation, but on the other hand, it leads to a progressive H2O2 accumulation that ultimately results in apoptosis. These results indicate that the anti- and pro-apoptotic effects of Rel/NF-kappaB factors are not necessarily alternative but can occur successively in the same cell, via the up-regulation of the same target gene.