Metallothionein degradation: metal composition as a controlling factor

Degradation of the cadmium (Cd)-induced protein, metallothionein (MT) was studied in rat liver and kidney. The half-times (t1/2s) for degradation of the protein were found to vary according to the concentration of Cd in the tissues. In animals containing high Cd2+ concentrations, the t1/2 of degradation was significantly longer than in low Cd2+ animals. There were no significant differences in degradation times between liver and kidney. Purification of the MT by anion exchange chromatography revealed two species which had, in the liver at least, different degradation times. Since the metal content of the MTs did not vary throughout the time course of the experiment, it is proposed that the rate of degradation and hence the turnover of the protein is influenced by the ratio of Cd2+ to other bound cations (e.g. Zn2+ and Cu2+). Thus, the Cd/Zn ratio in the liver and the Cd/Cu ratio in the kidney determine the respective rates of degradation and hence turnover of the protein.