Metallothionein turnover in mammalian cells. Implications in metal toxicity

Metallothioneins are low molecular weight, cysteine-rich proteins believed to participate in metal detoxification. Turnover of Cd-, Zn-, and Au-induced metallothionein was studied in a Chinese hamster ovary cell line which was resistant to Cd and the Au-containing drug auranofin. Cd, Zn, and Au were potent inducers of metallothionein mRNA and resulted in accumulation of approximately equal amounts of mRNA. Pulse-chase studies with [35S]cysteine revealed that the half-life of Au-, Zn-, and Cd-induced metallothionein was 0.75, 10, and 24 h, respectively. The differences in the half-life of metallothionein may be related to the tertiary structure of metal-metallothionein complexes. These results have implications in the mechanism of resistance to gold compounds.