Evidence that reactive oxygen species do not mediate NF-κB activation
Evidence that reactive oxygen species do not mediate NF-κB activation
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DOI：
10.1093/emboj/cdg332
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发表时间：
2003-07-01
期刊：
影响因子：
11.4
通讯作者：
Kikugawa, K
中科院分区：
文献类型：
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作者：
Hayakawa, M;Miyashita, H;Kikugawa, K
据推测，ROS可能是导致核因子-kappaB活化的第二信使。这一假说主要是基于N-乙酰-L-半胱氨酸和吡咯烷二硫代氨基甲酸酯这两种被认为是潜在的抗氧化剂的化合物可以抑制多种细胞类型中的核因子-kappaB的激活。在这里，我们揭示了NAC和PDTC都抑制了NF-kappaB的激活，而不依赖于抗氧化功能。NAC通过降低肿瘤坏死因子受体与肿瘤坏死因子的亲和力，选择性地阻断肿瘤坏死因子诱导的信号传导。PDTC抑制无细胞系统中IkappaB-泛素连接酶的活性，在无细胞系统中，不存在细胞外刺激调节的ROS产生。此外，我们提供的证据表明，通过RAC/NADPH氧化酶产生的内源性ROS并不介导NF-kappaB信号，而是降低其激活的幅度。
It has been postulated that reactive oxygen species (ROS) may act as second messengers leading to nuclear factor (NF)-kappaB activation. This hypothesis is mainly based on the findings that N-acetyl-l-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), compounds recognized as potential antioxidants, can inhibit NF-kappaB activation in a wide variety of cell types. Here we reveal that both NAC and PDTC inhibit NF-kappaB activation independently of antioxidative function. NAC selectively blocks tumor necrosis factor (TNF)-induced signaling by lowering the affinity of receptor to TNF. PDTC inhibits the IkappaB-ubiquitin ligase activity in the cell-free system where extracellular stimuli-regulated ROS production does not occur. Furthermore, we present evidence that endogenous ROS produced through Rac/NADPH oxidase do not mediate NF-kappaB signaling, but instead lower the magnitude of its activation.