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假定的双氢可的松受体的类固醇特异性:该受体并非11β-羟类固醇脱氢酶的证据

Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11betaHSD.

作者信息

Sheppard K E, Khoo K, Krozowski Z S, Li K X

机构信息

Baker Medical Research Institute, Melbourne, Victoria 8008, Australia 3181.

出版信息

Am J Physiol. 1998 Jul;275(1):E124-31. doi: 10.1152/ajpendo.1998.275.1.E124.

DOI:10.1152/ajpendo.1998.275.1.E124
PMID:9688883
Abstract

Recently, we identified a novel putative nuclear receptor in colonic crypt cells distinct from both mineralocorticoid receptor and glucocorticoid receptor, with high affinity for 11-dehydrocorticosterone (11-DHB) (33). In the present study, competitive nuclear binding assays demonstrated that this site has a unique steroid binding specificity that distinguishes it from other steroid receptors. Western blot analysis showed the presence of 11beta-hydroxysteroid dehydrogenase-2 (11betaHSD2) but not 11betaHSD1 in colonic crypt cells and showed that 11betaHSD2 was present in the nuclear pellet. Differences in steroid specificity between the putative DHB receptor and inhibition of 11betaHSD activity indicate that binding is not to the enzyme. Furthermore, modified Chinese hamster ovary cells transfected with the 11betaHSD2 gene express nuclear 11betaHSD2 but not a nuclear DHB binding site. In conclusion, these data support the existence of a novel nuclear DHB receptor in rat colon that is distinct from the classic steroid receptors and from both 11betaHSD1 and 11betaHSD2.

摘要

最近,我们在结肠隐窝细胞中鉴定出一种新型的假定核受体,它不同于盐皮质激素受体和糖皮质激素受体,对11-脱氢皮质酮(11-DHB)具有高亲和力(33)。在本研究中,竞争性核结合试验表明,该位点具有独特的类固醇结合特异性,使其与其他类固醇受体区分开来。蛋白质印迹分析显示结肠隐窝细胞中存在11β-羟基类固醇脱氢酶-2(11βHSD2),但不存在11βHSD1,并表明11βHSD2存在于核沉淀物中。假定的DHB受体之间的类固醇特异性差异以及11βHSD活性的抑制表明结合不是针对该酶的。此外,用11βHSD2基因转染的修饰中国仓鼠卵巢细胞表达核11βHSD2,但不表达核DHB结合位点。总之,这些数据支持在大鼠结肠中存在一种新型核DHB受体,它不同于经典类固醇受体以及11βHSD1和11βHSD2。

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引用本文的文献

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High salt intake down-regulates colonic mineralocorticoid receptors, epithelial sodium channels and 11β-hydroxysteroid dehydrogenase type 2.高盐摄入会下调结肠盐皮质激素受体、上皮钠通道和 11β-羟类固醇脱氢酶 2。
PLoS One. 2012;7(5):e37898. doi: 10.1371/journal.pone.0037898. Epub 2012 May 31.