METAL ION HOMEOSTASIS WITH EMPHASIS ON ZINC AND COPPER: POTENTIAL CRUCIAL LINK TO EXPLAIN THE NON-CLASSICAL ANTIOXIDATIVE PROPERTIES OF VITAMIN D AND MELATONIN

VIRNA MARTÍN GIMENÉZ; IVANA BERGAM; RUSSEL J. REITER; WALTER MANUCHA

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2021 vol. 281

0024-3205

Metal ion homeostasis is an essential physiological mechanism necessary for achieving an adequate balance of these ions´ concentrations in the different cellular compartments. This fact is of great importance because both an excess or a deficiency of cellular metal ion levels are usually equally harmful due to the exacerbated increase in oxidative stress that may occur in both cases. In this way, metal ion homeostasis ensures an equilibrium among multiple functions associated with the body´s antioxidative defence controlled by metallic micronutrients such as zinc and copper, some of the central regulators of redox processes. These metal ions significantly modulate the activity of some isoforms of superoxide dismutase (SOD) and other enzymes such as metallothioneins and ceruloplasmin, which are directly or indirectly involved in the regulation of redox homeostasis. Although it is well known that both melatonin and vitamin D has important roles as natural antioxidants through a different mechanism of action and signalling pathways, many times some of these effects are related to their actions on antioxidative processes dependent on metal ions. Thus, in addition to their classical antioxidative properties usually associated with mitochondrial effects, it was demonstrated that melatonin and vitamin D could modulate copper/zinc-dependent SOD expression and activity isoforms and regulate the genomic and non-genomic mechanisms related to the transport of both metal ions. Therefore, this review summarizes the main findings related to the crucial participation of zinc and copper in physiological antioxidative status and their relationship with the non-classical antioxidant effects of melatonin and vitamin D, suggesting a potential synergism among these four micronutrients.