Thioredoxin and glutaredoxin enhance the binding of L-triiodothyronine to its hepatic nuclear receptors.
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.
Takagi
S
S
Thyroid Research Laboratory, Mount Sinai Hospital Research Institute, Toronto, Ont., Canada.
Bhat
G B
GB
Hummel
B C
BC
Walfish
P G
PG
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D054477:Glutaredoxins; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010088:Oxidoreductases; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D013879:Thioredoxins / Q000494:pharmacology*; D014284:Triiodothyronine / Q000378:metabolism*
D001426:Bacterial Proteins; D054477:Glutaredoxins; D011506:Proteins; D014284:Triiodothyronine; D013879:Thioredoxins; D010088:Oxidoreductases