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糖皮质激素对人血红素加氧酶基因的下调作用及56b调控元件的鉴定

Downregulation of the human heme oxygenase gene by glucocorticoids and identification of 56b regulatory elements.

作者信息

Lavrovsky Y, Drummond G S, Abraham N G

机构信息

Rockefeller University, New York, New York 10021, USA.

出版信息

Biochem Biophys Res Commun. 1996 Jan 26;218(3):759-65. doi: 10.1006/bbrc.1996.0135.

DOI:10.1006/bbrc.1996.0135
PMID:8579587
Abstract

Several human heme oxygenase-1 promoter-driven chloramphenicol acetyltransferase constructs were examined in order to analyze promoter activity of the heme oxygenase-1 gene in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by interleukin-6. This induction was shown to be down-regulated by glucocorticoids. Chloramphenicol acetyltransferase assays revealed that the promoter region (56 base pair) between -180 and -120 was responsible for up-regulation by growth factors, as well as for glucocorticoid-directed down-regulation. The same DNA fragments was shown to bind nuclear factor(s) from endothelial cells treated with dexamethasone. Formation of DNA protein complexes peaked after a 6-hour treatment. The DNA fragment was found to contain a sequence recognized by the STAT 3/acute phase response factor.

摘要

为了分析血红素加氧酶-1基因在微血管内皮细胞中的启动子活性,对几种人血红素加氧酶-1启动子驱动的氯霉素乙酰转移酶构建体进行了检测。血红素加氧酶启动子活性被白细胞介素-6上调。这种诱导作用被证明会被糖皮质激素下调。氯霉素乙酰转移酶分析表明,-180至-120之间的启动子区域(56个碱基对)负责生长因子的上调以及糖皮质激素介导的下调。相同的DNA片段被证明能与用地塞米松处理的内皮细胞核因子结合。DNA-蛋白质复合物的形成在6小时处理后达到峰值。发现该DNA片段包含一个被信号转导子和转录激活子3/急性期反应因子识别的序列。

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