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首页> 外文期刊>The Journal of Steroid Biochemistry and Molecular Biology >The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements.
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The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements.

机译:线粒体是糖皮质激素作用的主要部位:糖皮质激素受体与线粒体DNA序列的相互作用显示出与核糖皮质激素响应元件的部分相似性。

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摘要

Six mitochondrial genome sequences, showing strong similarity to the glucocorticoid responsive element consensus sequence (GRE), four localized within the cytochrome c oxidase (COX) subunit I and II genes (GREs I-IV) and two within the D-loop region (GREs a and b) have been examined as binding sites of glucocorticoid receptor (GR) from rat liver cytosol. Purified GR from rat liver cytosol binds with high specificity to all potential mitochondrial GREs, as shown by filter retention and gel shift assays. Specific binding of protein(s), present in a mitochondrial extract from dexamethasone-induced mice, to all six putative mitochondrial GREs was also documented by the same methodology. Both purified GR and protein(s) from mitochondrial extract give the same band in the gel retardation assay. Using monospecific anti-glucocorticoid receptor polyclonal antibody (EP), a supershift of the gel retarded protein-DNA band was obtained. These results demonstrate that the mitochondrial genome sequences examined havecharacteristics of GREs, since they show the capacity to specifically bind the respective receptor protein. These findings support the hypothesis that the mitochondrial genome is a primary site of action of steroid and thyroid hormones (Sekeris C.E.: The mitochondrial genome: a possible primary site of action of steroid hormones, In vivo 4 (1990) 317-320).
机译:六个线粒体基因组序列显示出与糖皮质激素反应元件共有序列(GRE)的高度相似性,四个位于细胞色素C氧化酶(COX)I和II亚基基因(GREs I-IV)内,两个位于D环区域(GREs)已检查a和b)作为大鼠肝细胞溶胶中糖皮质激素受体(GR)的结合位点。从大鼠肝细胞质中纯化得到的GR与所有潜在的线粒体GRE具有高特异性结合,如过滤器保留和凝胶位移分析所示。地塞米松诱导的小鼠的线粒体提取物中存在的蛋白质与所有六种假定的线粒体GRE的特异性结合也通过相同的方法进行了证明。来自线粒体提取物的纯化GR和蛋白质在凝胶阻滞分析中均显示相同的条带。使用单特异性抗糖皮质激素受体多克隆抗体(EP),获得了凝胶阻滞蛋白-DNA条带的超移。这些结果表明,所检查的线粒体基因组序列具有GREs的特性,因为它们显示出特异性结合各自受体蛋白的能力。这些发现支持以下假设:线粒体基因组是类固醇和甲状腺激素的主要作用部位(Sekeris C.E .:线粒体基因组:类固醇激素的可能的主要作用部位,In vivo 4(1990)317-320)。

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