Function of metallothionein in gene expression and signal transduction: Newly found protective role of metallothionein

A heavy-metal-binding protein, metallothionein (MT), is induced by heavy metal overload and reactive oxygen species (ROS). The metals and ROS are rendered harmless by binding to NIT or by oxidizing MT, respectively. This is a well-known role of MT. MT is also induced by glucocorticoids and cytokines. Induced MT may increase intracellular free zinc and modulate the activity of transcription factors. Changes in MT levels are thought to help in adaptation to changes in environmental conditions. NIT modulates inflammatory reactions, including lipopolysaccharide (LPS)-induced expression of cytokines, nitric oxide production from macrophages in response to LPS, and resistance to LPS/D-galactosamine-induced lethality. In this review, we focus on a newly found protective role of MT, which acts mainly via changes in intracellular zinc levels or modulation of gene expression.