RESUMO
Purpose: We proposed that zinc (Zn) deposition in deciduous teeth would be a timed record of exposure to this essential micronutrient over very early life. We tested this hypothesis by gathering information on the maternal and child's diet during pregnancy and early infancy and measuring mineral deposition in the dentine at points during deciduous tooth development. Methods: We developed a short food frequency questionnaire (S-FFQ) to record consumption of food containing Zn during pregnancy and over the first year of life of the child in an Indonesian population. Zn, Sr and Ca were measured by laser ablation ICP-MS in a series of points across the developmental timeline in deciduous teeth extracted from 18 children undergoing the process as part of dental treatment whose mothers completed the SFFQ. Mothers and children were classified into either high Zn or low Zn groups according to calculated daily Zn intake. Results: The Zn/Sr ratio in dentine deposited over late pregnancy and 0-3 months post-partum was higher (p < 0.001, 2-way ANOVA; p < 0.05 by Holm-Sidak post hoc test) in the teeth of children of mothers classified as high Zn consumers (n = 10) than in children of mothers classified as low Zn consumers (n = 8). Conclusion: The S-FFQ was validated internally as adequately accurate to measure zinc intake retrospectively during pregnancy and post-partum (â¼7 years prior) by virtue of the correlation with measurements of zinc in deciduous teeth. The ratio of Zn/Sr in deciduous teeth appears to be a biomarker of exposure to zinc nutrition during early development and offers promise for use as a record of prior exposure along a timeline for research studies and, potentially, to identify individuals at heightened risk of detrimental impacts of poor early life zinc nutrition on health in later life and to implement preventative interventions.
RESUMO
Only a small number of genes are known direct targets of the zinc-responsive transcription factor MTF1; therefore, the aim of this study was to gain a more complete understanding of the MTF-1 regulated zinc-responsive component of the transcriptome. A targeted siRNA was used to deplete MTF1 expression in the human intestinal cell line Caco-2. We predicted that the response to zinc of direct MTF1 target genes would be abrogated by MTF1 knockdown. Surprisingly, a greater number of genes were regulated by zinc following MFT1 knockdown, and most genes that responded to zinc under both control and MTF1-depleted conditions had an augmented response in the latter condition. Exceptions were the zinc effluxer ZnT1 and a suite of metallothionein genes, suggesting that responses of other genes to zinc are usually buffered by increases in these proteins. We propose that MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content. We tested and validated this model by overexpressing metallothionein and observing the predicted curtailment in response of the zinc-repressed SLC30A5 (ZnT5) promoter. The model provides the framework for an integrated understanding of cellular zinc homeostasis. Because MTs can bind metals other than zinc, this framework links with overall cellular metal homeostasis.