Proof that the endogenous, heat-stable glucocorticoid receptor-activating factor is thioredoxin.
Proof that the endogenous, heat-stable glucocorticoid receptor-activating factor is thioredoxin.
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DOI：
10.1016/s0021-9258(18)89698-3
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发表时间：
1985-01
期刊：
影响因子：
--
通讯作者：
J F Grippo;A. Holmgren;W B Pratt
中科院分区：
文献类型：
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作者：
J F Grippo;A. Holmgren;W B Pratt
用木炭提取的大鼠肝细胞液可以灭活糖皮质激素结合能力，受体可以通过内源性还原系统重新激活到类固醇结合状态，该系统利用NADPH和MR=12,000，热稳定的内源性胞浆蛋白(Grippo，J.F.，Tienrungroj，W.，Dahmer，M.K.，Housley，P.R.和Pratt，W.B.J.Biol)。化学。258、13658-13664)。在这篇文章中，我们证明了大鼠肝脏糖皮质激素受体从非结合形式到类固醇结合形式的依赖NADPH的转换可以被提纯的大鼠肝脏硫氧还蛋白还原酶或硫氧还蛋白的抗血清以免疫特异性的方式阻断。硫氧还蛋白还原酶抗血清对硫氧还蛋白还原酶的抑制作用可被二硫苏糖醇克服，或通过加入纯化的硫氧还蛋白还原酶来克服。这些观察结果证明，内源性糖皮质激素受体激活因子是硫氧还蛋白，内源性受体激活系统产生糖皮质激素受体类固醇结合构象所需的酶是硫氧还蛋白还原酶。
Extraction of rat liver cytosol with charcoal inactivates glucocorticoid-binding capacity and receptors can be reactivated to the steroid-binding state by an endogenous reducing system utilizing NADPH and a Mr = 12,000, heat-stable, endogenous, cytosolic protein (Grippo, J. F., Tienrungroj, W., Dahmer, M. K., Housley, P. R., and Pratt, W. B. (1983) J. Biol. Chem. 258, 13658-13664). In this paper we show that NADPH-dependent conversion of the rat liver glucocorticoid receptor from a nonbinding to a steroid-binding form is blocked in an immune-specific manner by antisera raised against purified rat liver thioredoxin reductase or thioredoxin. The inhibition produced by thioredoxin reductase antiserum may be circumvented by dithiothreitol or overcome by addition of purified thioredoxin reductase. These observations prove that the endogenous glucocorticoid receptor-activating factor is thioredoxin and that the enzyme required for generating the steroid-binding conformation of the glucocorticoid receptor by the endogenous receptor-activating system is thioredoxin reductase.