ArticleJournal of molecular medicine (Berlin, Germany)2006
Silencing of ZnT-1 expression enhances heavy metal influx and toxicity.
Article in Journal of molecular medicine (Berlin, Germany), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 79 citations in OpenAlex.
- Nanomolar Cadmium Disrupts Neurotransmitter Release Timing via a ROS-dependent Mechanism at the Mouse Neuromuscular Junction: Modulation by Nanomolar ZnNeurochemical research · 2026Article
- ZIP-ZnT1 complexes mediate a local ZnCellular and molecular life sciences : CMLS · 2026Article
- Modulation of ZnT-1 by Let7a unveils a therapeutic potential in amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium.International journal of molecular sciences · 2024Review
- Review
- Cadmium alters whole animal ionome and promotes the re-distribution of iron in intestinal cells ofFrontiers in physiology · 2023Article
- Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.Neuroscience letters · 2022Article
- Zinc in Cognitive Impairment and Aging.Biomolecules · 2022Review
- A novel chronic in vivo oral cadmium exposure-washout mouse model for studying cadmium toxicity and complex diabetogenic effects.Toxicology and applied pharmacology · 2022Article
- Sex differences in the effects of whole-life, low-dose cadmium exposure on postweaning high-fat diet-induced cardiac pathogeneses.The Science of the total environment · 2022Article
- Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells.Biological trace element research · 2021Article
- Zinc, Zinc Transporters, and Cadmium Cytotoxicity in a Cell Culture Model of Human Urothelium.Toxics · 2021Article
- Zinc as a countermeasure for cadmium toxicity.Acta pharmacologica Sinica · 2021Review
- Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia.International journal of molecular sciences · 2020Article
- Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.Scientific reports · 2017Article
- Zinc transporter-1 concentrates at the postsynaptic density of hippocampal synapses.Molecular brain · 2014Article
- Redox regulation of intracellular zinc: molecular signaling in the life and death of neurons.Antioxidants & redox signaling · 2011Review
- Modulation of neuronal signal transduction and memory formation by synaptic zinc.Frontiers in behavioral neuroscience · 2011Article
- The ß subunit of voltage-gated Ca2+ channels.Physiological reviews · 2010Review
- Zinc toxicity to aminergic neurotransmitters in rat brain.Toxicology international · 2010Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ZnT-1 reduces intracellular zinc accumulation and confers resistance against cadmium toxicity by a mechanism which is still unresolved. A functional link between the L-type calcium channels (LTCC) and ZnT-1 has been suggested, indicating that ZnT-1 may regulate ion permeation through this pathway. In the present study, immunohistochemical analysis revealed a striking overlap of the expression pattern of LTCC and ZnT-1 in cardiac tissue and brain. Using siRNA to silence ZnT-1 expression, we then assessed the role of ZnT-1 in regulating cation permeation through the L-type Ca(2+) channels in cells that are vulnerable to heavy metal permeation. Transfection of cortical neurons with ZnT-1 siRNA resulted in about 70% reduction of ZnT-1 expression and increased Ca(2+) influx via LTCC by approximately fourfold. Moreover, ZnT-1 siRNA transfected neurons showed approximately 30% increase in synaptic release, monitored using the FM1-43 dye. An increased cation influx rate, through the LTCC, was also recorded for Zn(2+) and Cd(2+) in cells treated with the ZnT-1 siRNA. Furthermore, Cd(2+)-induced neuronal death increased by approximately twofold after transfection with ZnT-1 siRNA. In addition, ZnT-1 siRNA transfection of the ovarian granulosa cell line, POGRS1, resulted in a twofold increase in Cd(2+) influx rate via the LTCC. Finally, a robust nimodipine-sensitive Cd(2+) influx was observed using a low extracellular Cd(2+) concentration (5 muM) in neurons and testicular slice cultures, attesting to the relevance of the LTCC pathway to heavy metal toxicity. Taken together, our results indicate that endogenously-expressed ZnT-1, by modulating LTCC, has a dual role: regulating calcium influx, and attenuating Cd(2+) and Zn(2+) permeation and toxicity in neurons and other cell types.
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