Figure 6. Zinc in the regulation of redox signaling.
NO, H2O2, oxidized GSH, and other oxidant species can modify zinc (Zn2+) thiolates leading to zinc release from MT and other proteins. Those species can exert reversible or irreversible chemical modifications of thiol residues (the formation of a disulfide is exemplified in this figure). If the protein is involved in signaling (e.g. transcription factor (TF), kinase, phosphatase, tubulin) a change in activity would lead to changes in signaling modulation. On the other hand, the released zinc can per se regulate transcription factors and the activity of phosphatases and kinases involved in signaling. A direct modulation of transcription factor Nrf2 by zinc will affect GSH synthesis, which would indirectly affect cell redox homeostasis and redox signaling. Zinc is part of the antioxidant network protecting biological systems from oxidative stress. Protein thiol-bound zinc participates in redox sensing. Zinc regulates proteins directly or indirectly involved in redox homeostasis. Zinc can modulate redox signaling through multiple mechanisms. NO and oxidants release zinc bound to sulfur clusters.