Brach M A, Hass R, Sherman M L, Gunji H, Weichselbaum R, Kufe D
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
J Clin Invest. 1991 Aug;88(2):691-5. doi: 10.1172/JCI115354.
Recent studies have demonstrated that treatment of mammalian cells with ionizing radiation is associated with activation of gene expression. Although the signal transduction pathways stimulated by ionizing radiation remain unclear, our previous findings indicate that radiation induces specific genes at the transcriptional level. The present work has examined the effects of ionizing radiation on the transcription factor NF-kappa B. The results demonstrate that ionizing radiation activates DNA binding of nuclear factor (NF)kappa B. This effect was detectable at 2 grays (Gy) and reached a maximum at 5-20 Gy. At a dose of 20 Gy, the increase in NF-kappa B binding activity was maximal at 2-4 h and then declined to pretreatment levels. The results also demonstrate that ionizing radiation transiently increases NF-kappa B mRNA levels. However, the finding that induction of NF-kappa B binding to DNA occurs in the presence of cycloheximide indicates that ionizing radiation activates preexisting NF-kappa B protein. NF-kappa B exists as a cytoplasmic protein before activation. Thus, our results suggest that ionizing radiation induces transduction pathways which include cytoplasmic signaling events.
最近的研究表明,用电离辐射处理哺乳动物细胞与基因表达的激活有关。尽管电离辐射刺激的信号转导途径仍不清楚,但我们之前的研究结果表明,辐射在转录水平上诱导特定基因。目前的工作研究了电离辐射对转录因子NF-κB的影响。结果表明,电离辐射激活了核因子(NF)κB的DNA结合。这种效应在2戈瑞(Gy)时即可检测到,并在5-20 Gy时达到最大值。在20 Gy的剂量下,NF-κB结合活性在2-4小时时增加到最大值,然后下降到预处理水平。结果还表明,电离辐射会短暂增加NF-κB mRNA水平。然而,在存在环己酰亚胺的情况下诱导NF-κB与DNA结合的发现表明,电离辐射激活了预先存在的NF-κB蛋白。NF-κB在激活前以细胞质蛋白的形式存在。因此,我们的结果表明,电离辐射诱导了包括细胞质信号事件在内的转导途径。