Induction of cadmium-thionein in isolated rat liver cells

Abstract

The uptake of cadmium by isolated liver cells was linearly related to the cadmium concentration to which the cells were exposed in the medium. Cadmium-treated cells synthesized proteins de novo with the characteristics of cadmium-thionein induced in the liver ofcadmium-treated animals. Thionein from liver cells incorporated cadmium and[35S]cysteine, had a Vl/Vo (Sephadex G-50) of 1.8-1.9, and was separated into two subfractions by DEAE-cellulose ion-exchange chromatography. Cycloheximide and actinomycin D when added after a cadmium exposure prevented the synthesis ofthionein. However, addition of actinomycin D after synthesis had started only decreased the total amount of thionein synthesized. The concentration of cadmium to which the cells were exposed affected the amount of cadmium-thionein synthesized in 6h. The maximum response occurred when cells were exposed to 0.5,ug of cadmium/ml; at higher metal concentrations the total amount of cadmium-thionein synthesized declined. The system described in the present paper can be used to study the mode of metal toxicity and the mechanism of cadmium-thionein synthesis.

Inducible Cadmium Binding Complexes of Cabbage and Tobacco

“…The induction of the thionein ligand in animals has been demonstrated in several laboratories after simultaneous administration of 112Cd and 3S or [35S]cysteine (9,13). Similar experiments were performed here with 112Cd and 35S.…”

Cadmium, an Effector in the Synthesis of Thionein

“…In isolated cells exposed to 1 ,ug Cd/ml, cadmium uptake did not vary significantly with time of incubation; however, if the cadmium concentrations were varied metal uptake increased linearly with increasing cadmium concentrations (19). These observations suggested that the cells absorbed the metal by diffusion, an equilibrium was established fairly rapidly after exposure, and the higher the concentration to which cells were exposed, the more metal they absorbed (19).…”

“…The isolation of cadmium thionein and the measurements of cadmium and 35S-cysteine were carried out as described earlier (19,20). and glass-distilled water.…”

“…We have previously suggested that the synthesis of thionein may be regulated in liver by cadmium acting as an extracellular effector (16)(17)(18)(19)(20), according to a model which can be summarized as follows. The metal induces thionein in the absence of synergistic and antagonistic effects between different tissues and organs.…”

Effects of Cadmium on Polyribosome Sedimentation Pattern in Mouse Liver

“…It was proposed that cadmium induces its synthesis by stimulating a specific mRNA synthesis (Squibb and Cousins, 1974;Hidalgo et al, 1978). The immediate effect of cadmium in liver is inhibition of the overall RNA-polymerase activity and protein synthesis (Hidalgo et ai.…”