Tanaka H, Makino Y, Hiramoto M, Handa H, Makino I
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Eur J Pharmacol. 1995 Oct 15;291(2):121-7. doi: 10.1016/0922-4106(95)90133-7.
We examined the effects of the novel benzoquinone derivative (2E)-3-[5-(2,3-dimethoxy-o-methyl-1,4-benzoquinoyl)]-2-nonyl -2-propenoic acid, E3330, on the functional activity of the glucocorticoid receptors. For that purpose we used a cloned CHOpMTGR cells, in which human glucocorticoid receptor cDNA was stably transfected and glucocorticoid receptor was expressed at high levels. After treatment of CHOpMTGR cells with E3330, neither the ligand binding activity nor immunoreactivity of the glucocorticoid receptor was affected. Moreover, E3330 did not affect the sequence-specific DNA binding activity of partially-purified glucocorticoid receptor in vitro. However, a glucocorticoid-inducible promoter was activated by E3330 in a dose-dependent fashion in the presence of the synthetic ligand dexamethasone. Interestingly, E3330 increased nuclear translocation of the glucocorticoid receptor in a ligand-independent fashion, indicating that E3330, through facilitation of the translocation of the glucocorticoid receptor, augments glucocorticoid-mediated gene transcription.
我们研究了新型苯醌衍生物（2E）-3-[5-(2,3-二甲氧基-邻甲基-1,4-苯醌酰基)]-2-壬基-2-丙烯酸（E3330）对糖皮质激素受体功能活性的影响。为此，我们使用了克隆的CHOpMTGR细胞，其中人糖皮质激素受体cDNA被稳定转染且糖皮质激素受体高水平表达。用E3330处理CHOpMTGR细胞后，糖皮质激素受体的配体结合活性和免疫反应性均未受影响。此外，E3330在体外不影响部分纯化的糖皮质激素受体的序列特异性DNA结合活性。然而，在合成配体地塞米松存在的情况下，E3330以剂量依赖的方式激活了糖皮质激素诱导型启动子。有趣的是，E3330以不依赖配体的方式增加了糖皮质激素受体的核转位，表明E3330通过促进糖皮质激素受体的转位增强了糖皮质激素介导的基因转录。
