Datta R, Taneja N, Sukhatme V P, Qureshi S A, Weichselbaum R, Kufe D W
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2419-22. doi: 10.1073/pnas.90.6.2419.
The cellular response to ionizing radiation includes induction of the early growth response 1 gene (EGR1). The present work has examined the involvement of reactive oxygen intermediates (ROIs) in this response. Exposure of human HL-525 cells, an HL-60 subclone deficient in protein kinase C-mediated signaling, to both ionizing radiation and H2O2 was associated with increases in EGR-1 transcripts. These increases in EGR-1 expression were inhibited by the antioxidant N-acetyl-L-cysteine (NAC). Nuclear run-on assays demonstrate that NAC inhibits the activation of EGR1 transcription by these agents. Previous studies have shown that induction of EGR1 by x-rays is conferred by serum response or CC(A/T)6GG (CArG) elements. The present studies demonstrate similar findings with H2O2 and the finding that activation of the EGR1 promoter region containing CArG elements is abrogated by NAC. Moreover, we show that NAC inhibits the ability of a single CArG box to confer x-ray and H2O2 inducibility when linked to a heterologous promoter. Taken together, these findings indicate that ROIs induce EGR1 transcription by activation of CArG elements.
细胞对电离辐射的反应包括早期生长反应1基因（EGR1）的诱导。目前的研究探讨了活性氧中间体（ROIs）在此反应中的作用。将人HL-525细胞（一种缺乏蛋白激酶C介导信号传导的HL-60亚克隆）暴露于电离辐射和过氧化氢中，与EGR-1转录本的增加有关。EGR-1表达的这些增加被抗氧化剂N-乙酰-L-半胱氨酸（NAC）抑制。核转录分析表明，NAC抑制这些试剂对EGR1转录的激活。先前的研究表明，X射线诱导EGR1是由血清反应元件或CC(A/T)6GG（CArG）元件介导的。目前的研究表明，过氧化氢也有类似的发现，并且含有CArG元件的EGR1启动子区域的激活被NAC消除。此外，我们表明，当与异源启动子连接时，NAC抑制单个CArG框赋予X射线和过氧化氢诱导性的能力。综上所述，这些发现表明ROIs通过激活CArG元件诱导EGR1转录。
