ArticleProceedings of the National Academy of Sciences of the United States of America2010
STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of ZnT2 (Slc30a2) in pancreatic acinar cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review.Advances in nutrition (Bethesda, Md.) · 2016Pooled it
- Extreme QTL mapping enables the identification of novel zinc toxicity response loci in Drosophila melanogaster.Genetics · 2025Article
- New insights into the role of metallothioneins in obesity and diabetes.International journal of obesity (2005) · 2025Review
- Roles of zinc and zinc transporters in development, progression, and treatment of inflammatory bowel disease (IBD).Frontiers in nutrition · 2025Review
- The zinc transporter Slc30a1 (ZnT1) in macrophages plays a protective role against attenuatedeLife · 2024Article
- NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.Antioxidants (Basel, Switzerland) · 2024Article
- Upregulation of Intracellular Zinc Ion Level after Differentiation of the Neural Stem/Progenitor Cells In Vitro with the Changes in Gene Expression of Zinc Transporters.Biological trace element research · 2024Article
- Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review.Nutrients · 2024Review
- Role of zinc in health and disease.Clinical and experimental medicine · 2024Review
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Regulation of anti-tumor immunity by metal ion in the tumor microenvironment.Frontiers in immunology · 2024Review
- Adipocyte STAT5 (signal transducer and activator of transcription 5) is not required for glucocorticoid-induced metabolic dysfunction.American journal of physiology. Endocrinology and metabolism · 2023Article
- Transcriptional Regulation and Protein Localization of Zip10, Zip13 and Zip14 Transporters of Freshwater Teleost Yellow CatfishInternational journal of molecular sciences · 2022Article
- Review
- Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms.Nutrients · 2021Review
- The effect of zinc deficiency and iron overload on endocrine and exocrine pancreatic function in children with transfusion-dependent thalassemia: a cross-sectional study.BMC pediatrics · 2021Article
- Zinc Signaling in the Mammary Gland: For Better and for Worse.Biomedicines · 2021Review
- Gawky modulates MTF-1-mediated transcription activation and metal discrimination.Nucleic acids research · 2021Article
- Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.EMBO molecular medicine · 2020Article
- Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The exocrine pancreas plays an important role in endogenous zinc loss by regulating excretion into the intestinal tract and hence influences the dietary zinc requirement. The present experiments show that the zinc transporter ZnT2 (Slc30a2) is localized to the zymogen granules and that dietary zinc restriction in mice decreased the zinc concentration of zymogen granules and ZnT2 expression. Excess zinc given orally increased ZnT2 expression and was associated with increased pancreatic zinc accumulation. Rat AR42J acinar cells when induced into a secretory phenotype, using the glucocorticoid analog dexamethasone (DEX), exhibited increased ZnT2 expression and labile zinc as measured with a fluorophore. DEX administrated to mice also induced ZnT2 expression that accompanied a reduction of the pancreatic zinc content. ZnT2 promoter analyses identified elements required for responsiveness to zinc and DEX. Zinc regulation was traced to a MRE located downstream from the ZnT2 transcription start site. Responsiveness to DEX is produced by two upstream STAT5 binding sites that require the glucocorticoid receptor for activation. ZnT2 knockdown in the AR42J cells using siRNA resulted in increased cytoplasmic zinc and decreased zymogen granule zinc that further demonstrated that ZnT2 may mediate the sequestration of zinc into zymogen granules. We conclude, based upon experiments with intact mice and pancreatic acinar cells in culture, that ZnT2 participates in zinc transport into pancreatic zymogen granules through a glucocorticoid pathway requiring glucocorticoid receptor and STAT5, and zinc-regulated signaling pathways requiring MTF-1. The ZnT2 transporter appears to function in a physiologically responsive manner involving entero-pancreatic zinc trafficking.
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