Mohan N, Meltz M L
Department of Radiology, University of Texas Health Science Center, San Antonio 78284-7800.
Radiat Res. 1994 Oct;140(1):97-104.
Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the kappa B transcription regulator in mitogen- or cytokine-stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca(++)-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-kappa B in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kappa B activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-dose ionizing radiation (0.1-2.0 Gy) activates kappa B transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-kappa B by low-dose ionizing radiation can be inhibited considerably by the antioxidant N-acetyl-L-cysteine, indicating that at least the major part of the activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the kappa B elements which in turn can serve as response elements for oxidant stress.
活性氧中间体（ROIs）已被发现是有丝分裂原或细胞因子刺激的细胞中κB转录调节因子激活过程中的信使，其作用与多种其他机制协同或独立发挥；这些机制包括依赖钙离子（Ca(++)）和依赖蛋白激酶C（PKC）的细胞质信号通路。我们最近报道低剂量电离辐射可在人淋巴母细胞244B细胞中诱导核因子κB（NF-κB）。由于电离辐射在细胞中产生自由基，我们研究了电离辐射产生的ROIs是否诱导NF-κB活性，以及它们是否通过与用佛波酯（PMA）或过氧化氢（H2O2）处理的细胞类似的机制来诱导。结果不仅证实了我们实验室之前的观察结果，即低剂量电离辐射（0.1 - 2.0 Gy）可短暂激活κB转录因子，在0.5 Gy照射时诱导作用最大，而且从机制上证明了低剂量电离辐射对NF-κB的激活可被抗氧化剂N-乙酰-L-半胱氨酸显著抑制，这表明至少激活过程的主要部分是由ROIs介导的。这些发现支持了ROIs可调节κB元件的观点，而κB元件反过来又可作为氧化应激的反应元件。
