Reactive oxygen species (ROS) has been implicated as an inducer of NF-kappaB activity in numbers of cell types where exposure of cells to ROS such as H(2)O(2) leads to NF-kappaB activation. In contrast, exposure to oxidative stress in certain cell types induced reduction of tumor necrosis factor (TNF)- induced NF-kappaB activation. And various thiol-modifying agents including gold compounds and cyclopentenone prostaglandins inhibit NF-kappaB activation by blocking IkappaB kinase (IKK). To understand such conflicting effect of oxidative stress on NF- kappakB activation, HeLa cells were incubated with H(2)O(2) or diamide and TNF-induced expression of NF-kappaB reporter gene was measured. NF-kappaB activation was significantly blocked by these oxidizing agents, and the inhibition was accompanied with reduced nuclear NF-kappaB and inappropriate cytosolic IkappaB degradation. H(2)O(2) and diamide also inhibited IKK activation in HeLa and RAW 264.7 cells stimulated with TNF and lipopolysaccharide, respectively, and directly blocked IKK activity in vitro. In cells treated with H(2)O(2) alone, nuclear NF-kappaB was induced after 2 h without detectable degradation of cytosolic IkappaBalphaa or activation of IKK. Our results suggest that ROS has a dual effect on NF-kappaB activation in the same HeLa cells: it inhibits acute IKK-mediated NF-kappakB activation induced by inflammatory signals, while longer-term exposure to ROS induces NF-kappaB activity through an IKK-independent pathway.

中文翻译：

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氧化应激对HeLa细胞中NF-κB活化的双重影响。

活性氧（ROS）已被暗示在细胞暴露于诸如H（2）O（2）等ROS导致NF-kappaB活化的细胞类型中作为NF-kappaB活性的诱导剂。相反，在某些细胞类型中暴露于氧化应激会导致肿瘤坏死因子（TNF）诱导的NF-κB活化减少。包括金化合物和环戊烯酮前列腺素在内的各种硫醇修饰剂可通过阻断IkappaB激酶（IKK）来抑制NF-kappaB的活化。为了了解这种氧化应激对NF-κB活化的冲突作用，将HeLa细胞与H（2）O（2）或二酰胺一起孵育，并测量TNF诱导的NF-κB报道基因表达。这些氧化剂可显着阻止NF-κB的活化，抑制作用伴随着核NF-κB的减少和胞质IkappaB的不适当降解。H（2）O（2）和二酰胺还分别抑制了TNF和脂多糖刺激的HeLa和RAW 264.7细胞中的IKK活化，并直接阻断了体外的IKK活性。在单独用H（2）O（2）处理的细胞中，核NF-κB在2小时后被诱导，没有可检测到的胞质IkappaBalphaa降解或IKK活化。我们的结果表明，ROS对相同HeLa细胞中的NF-κB活化具有双重作用：它抑制由炎症信号诱导的急性IKK介导的NF-κB活化，而长期暴露于ROS通过IKK诱导NF-κB活性。 -独立途径。分别用TNF和脂多糖刺激7个细胞，并在体外直接阻断IKK活性。在单独用H（2）O（2）处理的细胞中，核NF-κB在2小时后被诱导，没有可检测到的胞质IkappaBalphaa降解或IKK活化。我们的结果表明，ROS对相同HeLa细胞中的NF-κB活化具有双重作用：它抑制由炎症信号诱导的急性IKK介导的NF-κB活化，而长期暴露于ROS通过IKK诱导NF-κB活性。 -独立途径。分别用TNF和脂多糖刺激7个细胞，并在体外直接阻断IKK活性。在单独用H（2）O（2）处理的细胞中，核NF-κB在2小时后被诱导，没有可检测到的胞质IkappaBalphaa降解或IKK活化。我们的结果表明，ROS对相同HeLa细胞中的NF-κB活化具有双重作用：它抑制由炎症信号诱导的急性IKK介导的NF-κB活化，而长期暴露于ROS通过IKK诱导NF-κB活性。 -独立途径。