Reguation of mitochondrial transcription by activated glucocorticoid receptor

我们发现，反应氧（ROS）的产生与长期糖皮质激素治疗的骨骼肌线粒体功能障碍有关。此外，由于认为这种作用是糖皮质激素对线粒体的直接作用，因此在本研究中起草了进一步阐明这些观点的文件，并提供了一个有趣的结果。分析了皮质类固醇对各种培养细胞线粒体膜电位（Δ Δ m）、ROS产生及凋亡的影响。在分化细胞中，地塞米松的加入使活性氧产生增加，细胞凋亡增加，ΔΨm下降。而在SOD存在的条件下，这些变化均不明显。在增殖期细胞中，地塞米松使ROS产生增多，凋亡率随Δ λ m的增加而增加。SOD的存在使细胞内ROS的产生和凋亡的增加消失，但对Δ λ m的增加无影响。这些结果表明，激活的糖皮质激素受体在这些细胞中被移动到线粒体。此外，这些表明存在蛋白质来引导线粒体，尽管已经充分认识到活化的糖皮质激素受体在细胞核中转移。我们将糖皮质激素受体的GFP蛋白引入培养的细胞（COS，RD）中，以检查在地塞米松处理（1 × 10 - 6 × 10 - 6 μ M）下活化的糖皮质激素受体是否转移到线粒体<6-><-7>。除了细胞核之外，还在线粒体中观察到GFP信号。这有力地表明存在将糖皮质激素受体携带到线粒体的蛋白质。

We found that production of the reaction oxygen species (ROS) was related to the mitochondrial dysfunctional in the skeletal muscle with a long term glucocorticoid treatment. Furthermore, because it was thought that the effect was direct action for mitochondria by the glucocorticoid, it was drawn up to clarify these points in this study more, and an interesting result was provided. We analyzed the effect of corticosteroid on the mitochondria membrane potential (ΔΨm), generation of ROS and influence of the apoptosis in various kinds of cultured cells. In the differentiated cells, the dexamethasone addition let ROS generation and apoptosis increase with a fall of ΔΨm. These changes were not seen under the existence of SOD. In the proliferating cells, the dexamethasone let ROS generation and apoptosis increase with increase of ΔΨm. The ROS production and the increase of the apoptosis disappeared under the existence of SOD, but the increase of ΔΨm did not change. These results suggested that activated glucocorticoid receptors were moved to the mitochondria in these cells. Furthermore, these indicated the existence of protein to guide to the mitochondria although it had been well recognized that the activated glucocorticoid acceptor shifted in a nucleus. We introduced the GFP protein of the glucocorticoid acceptor into cultured cell (COS, RD) to examine whether an activated glucocorticoid acceptor shifted to mitochondria under dexamethasone treatment (1 x 10^<6-> x 10^<-7>M). GFP signals were observed in the mitochondria in addition to nuclei. This strongly suggested the existence of the protein which carried a glucocorticoid acceptor to mitochondria.