Metallothionein and its role in toxic metal regulation

1. Recent studies on regulation of metallothionein (MT) genes in higher animals and metallobiochemical interactions between MT and target molecules provide further support for a role of MT in metal detoxification. 2. New insights on regulation of MT gene expression via a Zn-sensitive inhibitor (35) coupled with the ''rescue'' hypothesis for metal detoxification by MT (19) provide the basis for a conceptual model for interpreting the significance of MT induction in response to toxic metals. In this model, induction of MT requires release of inhibition by Zn. The source of this Zn in cells exposed to other metals such as Cd is displacement of Zn by the toxic metal at Zn-binding intracellular target sites for metal toxicity. The newly formed metal-ligand complex can represent toxic interactions and be repaired by ZnMT through metal-metal exchange reactions. 3. Thus, induction of MT signifies prior toxic interactions between metals and their targets of toxicity and the onset of compensatory responses. Examples taken from the response of the molluse Crassostrea virginica are consistent with this model.