Effect of zinc(II) and other divalent cations on binding of 3,5,3'-triiodo-L-thyronine to nuclear receptors from cultured GC cells.
The effect of Zn(II) in 3,5,3'-triiodo-L-thyronine (T3) binding to nuclear receptors was studied in dialyzed 0.4 M NaCl extracts of nuclei from cultured GC cells. Addition of ZnCl2 to nuclear extracts resulted in a time- and concentration-dependent dissociation of T3 from nuclear receptors. Half-maximal dissociation occurred at 6 microM ZnCl2. Addition of ZnCl2 also resulted in a concentration-dependent inhibition of binding of T3 to nuclear receptors. Half-maximal inhibition of binding occurred at 1-3 microM ZnCl2. Scatchard analysis indicated that Zn(II) addition decreased kA and did not alter receptor concentration. These effects of Zn(II) were prevented when ZnCl2 was added to nuclear extracts in the presence of 5 mM EDTA or 5 mM dithiothreitol. Moreover, Zn(II)-induced inhibition of T3 binding was reversed by the addition of 5 mM EDTA. The inhibitory effect of Zn(II) on T3 binding seemed specific for nuclear receptors; no effect of Zn(II) on the binding of T3 to proteins in rat serum or GC cell cytosol or to rabbit anti-T3 serum was observed. Cd(II) had a similar concentration-dependent inhibition of T3 binding to nuclear receptors which was reversible. Our findings suggest that Zn(II) may play a role in T3 binding to nuclear receptors as well as its putative role in the binding of receptor to DNA.
Surks
M I
MI
Department of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Ramirez
I J
IJ
Shapiro
L E
LE
Kumara-Siri
M
M
D000818:Animals; D002413:Cations, Divalent; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
D002413:Cations, Divalent; D002712:Chlorides; D011988:Receptors, Thyroid Hormone; D017967:Zinc Compounds; D014284:Triiodothyronine; C016837:zinc chloride; D015032:Zinc