Zinc and the modulation of redox homeostasis

• Published in: Free radical biology & medicine Vol. 53; no. 9; pp. 1748 - 1759
• Main Author: Oteiza, Patricia I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2012
• Subjects: animal models; Animals; Antioxidant; Antioxidants - metabolism; Antioxidants - physiology; Coordination Complexes - metabolism; cysteine; Free radicals; functional properties; glutathione; Homeostasis; Humans; metabolism; Metalloproteins - metabolism; Metallothionein; Nitric oxide; nutrient deficiencies; oxidants; Oxidation-Reduction; Oxidative Stress; peroxides; Reactive Oxygen Species - metabolism; Redox homeostasis; Redox signaling; Signal Transduction; sulfur; Thiols; Zinc; Zinc - metabolism; Zinc - physiology; Oxidative stress; Thiols; JNK; PTP; RXR; Nrf2; NMDA; GSH; Free radicals; BDNF; VDR; MT; PKC; Akt; MAPK; Antioxidant; Redox signaling; Zinc; GCL; MOR; Redox homeostasis; Nitric oxide; Keap1; GPCR; NMDAR; Metallothionein; ERK
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2012.08.568

Zinc, a redox-inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintaining the cell redox balance through various mechanisms including: (i) the regulation of oxidant production and metal-induced oxidative damage; (ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione, and other thiol oxidant species; (iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and acts per se as a scavenging oxidant; (iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and (v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue dysfunction in cell and animal models of zinc deficiency highlight the relevant role of zinc in the preservation of cell redox homeostasis. However, although the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the molecules, targets, and mechanisms involved are still partially known and the subject of active research. [Display omitted] ► 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.