title: Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling.
abstract: Zinc is a nutritionally fundamental trace element, essential to the structure and function of numerous macromolecules, including enzymes regulating cellular processes and cellular signaling pathways. The mineral modulates immune response and exhibits antioxidant and anti-inflammatory activity. Zinc retards oxidative processes on a long-term basis by inducing the expression of metallothioneins. These metal-binding cysteine-rich proteins are responsible for maintaining zinc-related cell homeostasis and act as potent electrophilic scavengers and cytoprotective agents. Furthermore, zinc increases the activation of antioxidant proteins and enzymes, such as glutathione and catalase. On the other hand, zinc exerts its antioxidant effect via two acute mechanisms, one of which is the stabilization of protein sulfhydryls against oxidation. The second mechanism consists in antagonizing transition metal-catalyzed reactions. Zinc can exchange redox active metals, such as copper and iron, in certain binding sites and attenuate cellular site-specific oxidative injury. Studies have demonstrated that physiological reconstitution of zinc restrains immune activation, whereas zinc deficiency, in the setting of severe infection, provokes a systemic increase in NF-κB activation. In vitro studies have shown that zinc decreases NF-κB activation and its target genes, such as TNF-α and IL-1β, and increases the gene expression of A20 and PPAR-α, the two zinc finger proteins with anti-inflammatory properties. Alternative NF-κB inhibitory mechanism is initiated by the inhibition of cyclic nucleotide phosphodiesterase, whereas another presumed mechanism consists in inhibition of IκB kinase in response to infection by zinc ions that have been imported into cells by ZIP8.
authors.affiliation: Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland. m.gawel.87@gmail.com.
authors.forename: Magdalena
authors.identifier: http://orcid.org/0000-0002-8120-6785
authors.initials: M
authors.lastname: Jarosz
authors.affiliation: Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Olbert
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Wyszogrodzka
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Młyniec
authors.affiliation: Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D015032:Zinc
keywords: Inflammation; NF-κB signaling; Oxidative stress; Protein A20; ZIP8; Zinc