Takagi S, Bhat G B, Hummel B C, Walfish P G
Thyroid Research Laboratory, Mount Sinai Hospital Research Institute, Toronto, Ont., Canada.
Biochem Cell Biol. 1989 Aug;67(8):477-80. doi: 10.1139/o89-076.
The influence of thioredoxin and glutaredoxin on binding of L-triiodothyronine (T3) to the rat hepatic nuclear T3 receptor was compared with that of the exogenous activator dithiothreitol. Specific [125I]T3 binding, the affinity constant, Ka, and the maximal binding capacity, MBC, were measured using whole nuclei, solubilized preparations of receptor, and chromatographed nuclear receptor. Both the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH) and the glutaredoxin system (glutaredoxin, glutathione reductase, glutathione, and NADPH) increased specific binding of T3 to nuclei, solubilized receptor, and chromatographed receptor significantly. Compared with the values obtained in the absence of added thiol (Ka = 1.6 +/- 0.1 x 10(9) M-1, MBC = 1.7 +/- 0.06 pM), the thioredoxin and glutaredoxin systems increased Ka by 147 and 112%, respectively, while decreasing MBC by 51 and 45%, respectively, when chromatographed receptor was used. The same tendency was observed with solubilized receptor. However, dithiothreitol increased Ka without affecting MBC when solubilized receptor was used. These results, the first demonstration of endogenous disulphide reductant systems enhancing binding of T3 to its receptor, suggest that the thioredoxin and (or) glutaredoxin systems may modulate the physiological effects of thyroid hormone.
将硫氧还蛋白和谷氧还蛋白对L-三碘甲状腺原氨酸（T3）与大鼠肝细胞核T3受体结合的影响，与外源性激活剂二硫苏糖醇的影响进行了比较。使用完整细胞核、受体的可溶制剂和经色谱分离的核受体，测量了特异性[125I]T3结合、亲和常数Ka和最大结合容量MBC。硫氧还蛋白系统（硫氧还蛋白、硫氧还蛋白还原酶和NADPH）和谷氧还蛋白系统（谷氧还蛋白、谷胱甘肽还原酶、谷胱甘肽和NADPH）均显著增加了T3与细胞核、可溶受体和经色谱分离受体的特异性结合。与未添加硫醇时获得的值（Ka = 1.6 +/- 0.1 x 10(9) M-1，MBC = 1.7 +/- 0.06 pM）相比，当使用经色谱分离的受体时，硫氧还蛋白和谷氧还蛋白系统分别使Ka增加了147%和112%，而使MBC分别降低了51%和45%。使用可溶受体时也观察到了相同的趋势。然而，当使用可溶受体时，二硫苏糖醇增加了Ka但不影响MBC。这些结果首次证明了内源性二硫键还原系统增强了T3与其受体的结合，表明硫氧还蛋白和（或）谷氧还蛋白系统可能调节甲状腺激素的生理效应。
