Metallothionein Toxicology: Metal Ion Trafficking and Cellular Protection
The literature is replete with reports about the involvement of metallothionein in host defense against injurious chemical, biological, and physical agents. Yet, metallothionein's functional roles are still being debated. This review addresses the issues that have left the physiological significance of metallothionein in doubt and moves on to assess the MT's importance in cell toxicology. It is evident that the protein is broadly involved in protecting cells from injury due to toxic metal ions, oxidants, and electrophiles. Attention is focused on MT's structural and chemical properties that confer this widespread role in cell protection. Particular emphasis is placed on the implications of finding that metal ion unsaturated metallothionein is commonly present in many cells and tissues and the question, how does selectivity of reaction with metallothionein take place in the cellular environment that includes large numbers of competing metal binding sites and high concentrations of protein and glutathione sulfhydryl groups?