Abstract
Zinc is an element that is essential for cell proliferation and differentiation. Zinc is a structural constituent of a great number of proteins including metabolic enzymes, cellular signaling proteins and transcription factors. The total intracellular concentration of zinc and the intracellular concentration of the available ion are carefully controlled. The homeostasis of zinc is maintained by regulation of zinc uptake and elimination but also on the level of intracellular sequestration in zinc storing vesicles, soβcalled zincosomes, and by controlled nucleoβcytoplasmic distribution. A major tool of these processes is the zinc binding protein metallothionein which serves as a zinc storing protein and a zinc transporter to the nucleus in the course of cell cycling and differentiation. There is increasing evidence for a direct signaling function of zinc at all levels of cellular signal transduction. Zinc has been found to modulate cellular signal reception, second messenger metabolism, protein kinase and protein phosphatase activities, and it may activate or inhibit the DNA binding of transcription factors. Zinc ions specifically activate the transcription factor MTFβ1 which controls the expression of the genes for metallothionein and the zinc transporter protein ZnTβ1. There is increasing evidence that zinc ions function as modulators of cell proliferation and differentiation. Zinc becomes cytotoxic if its extracellular concentration exceeds the capacity of the zinc homeostatic system. Elevated extracellular zinc concentrations lead to a breakdown of the zinc transporting system of the plasma membrane. The resulting enhanced intracellular zinc concentration evokes the activation of programmed cell death (apoptosis), whereas at even more elevated zinc concentration, cell necrosis is the dominant form of cell death.