REACTIVE OXYGEN INTERMEDIATES TARGET CC(A/T)6GG SEQUENCES TO MEDIATE ACTIVATION OF THE EARLY GROWTH RESPONSE-1 TRANSCRIPTION FACTOR GENE BY IONIZING-RADIATION
REACTIVE OXYGEN INTERMEDIATES TARGET CC(A/T)6GG SEQUENCES TO MEDIATE ACTIVATION OF THE EARLY GROWTH RESPONSE-1 TRANSCRIPTION FACTOR GENE BY IONIZING-RADIATION
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DOI：
10.1073/pnas.90.6.2419
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发表时间：
1993-03-15
影响因子：
11.1
通讯作者：
KUFE, DW
中科院分区：
文献类型：
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作者：
DATTA, R;TANEJA, N;KUFE, DW
细胞对电离辐射的反应包括诱导早期生长反应1基因（EGR1）。目前的工作已经检查了活性氧中间体（roi）在这种反应中的参与。人类HL-525细胞（一种缺乏蛋白激酶c介导信号的HL-60亚克隆）暴露于电离辐射和H2O2与EGR-1转录物的增加有关。抗氧化剂n -乙酰半胱氨酸（NAC）抑制了EGR-1表达的增加。核运行试验表明NAC抑制这些药物对EGR1转录的激活。先前的研究表明，x射线诱导EGR1是由血清反应或CC(A/T)6GG （CArG）元素引起的。本研究在H2O2中也发现了类似的结果，并且发现含有CArG元素的EGR1启动子区域的激活被NAC所取消。此外，我们发现当NAC与异源启动子连接时，NAC抑制单个CArG盒赋予x射线和H2O2诱导性的能力。综上所述，这些发现表明roi通过激活CArG元件诱导EGR1转录。
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.