John Erica, et al.
Journal of translational medicine, 2010
Abstract
Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order.
Figures
Intracellular Zinc Levels Fall During Dendritic Cell Maturation. After the detection of LPS (Pathogen Associated PAMPs) by TLR4 and activation of TRIF, zinc importers (ZIPs) expression is diminished while transporters (ZNTs) expression is increased. The resulting decrease in intracellular zinc concentration promotes the surface expression of MHC-II and thus the maturation of DCs.
Localization and transport of zinc in a mammalian cell. Cellular localization and function of ZIP and ZNT zinc transporter family members. Arrows indicate the direction of zinc mobilization. ZIP1, 2 and 4 are induced in zinc deficient conditions, while ZNT-1 and 2 members are induced by zinc administration. In general zinc efflux is associated with enhanced susceptibility to apoptosis and higher levels with protection/autophagy.| PMID: | 21087493 |
|---|---|
| PMCID (Free PMC Article): | PMC3002329 |
| DOI: | 10.1186/1479-5876-8-118 |
| Category: | Immune |
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