Role of intracellular zinc in programmed cell death

Apoptosis is a type of cell death involved in several biological events during tissue development, remodelling or involution. It could be induced by several extracellular or intracellular stimuli with an important role for metals like zinc or calcium. Cellular zinc is described as an inhibitor of apoptosis, while its depletion induces death in many cell lines. Using different chemical tools like specific zinc-chelators or ionophores, it is possible to study and understand the mechanisms of programmed cell death induction. The decrease in intracellular zinc concentration induces a characteristic apoptosis with apoptotic bodies formation and nuclear DNA condensation and fragmentation. This zinc depletion activates the caspases-3, -8 and -9, responsible for the proteolysis of several target proteins like poly(ADP-ribose) polymerase or transcription factors. Zinc addition in cell culture medium prevents the apparition of morphological and biochemical signs induced by intracellular zinc chelation, but also by other apoptosis inducers like etoposide or tumour necrosis factor alpha (TNF alpha). However, excess of zinc can also be cytotoxic. The balance between life and cell death is maintained by several zinc channels, controlling the intracellular zinc movements and the free amount of the metal.