ArticleEnvironmental health perspectives2008
Fluoride induces endoplasmic reticulum stress and inhibits protein synthesis and secretion.
Article in Environmental health perspectives, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- A Systematic Review on the Association Between Water Fluoride Levels and Dental Fluorosis: Exploring the 'Halo Effect' and Confounding Environmental Factors.International journal of molecular sciences · 2026Pooled it
- Fluoride Induces Toxic Effects on the A549 Pulmonary Cell Line at Non-cytotoxic Concentrations.Biological trace element research · 2025Article
- Roles of calcium in ameloblasts during tooth development: A scoping review.Journal of Taibah University Medical Sciences · 2025Review
- Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure.Antioxidants (Basel, Switzerland) · 2024Article
- Article
- Unraveling molecular characteristic of fluoride neurotoxicity on U87 glial-like cells: insights from transcriptomic and proteomic approach.Frontiers in cellular neuroscience · 2023Article
- Advances in epidemiological status and pathogenesis of dental fluorosis.Frontiers in cell and developmental biology · 2023Review
- Cells Adapt to Resist Fluoride through Metabolic Deactivation and Intracellular Acidification.Chemical research in toxicology · 2022Article
- Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases.Frontiers in physiology · 2022Review
- Exogenous transforming growth factor-β1 prevents the inflow of fluoride to ameleoblasts through regulation of voltage-gated chloride channels 5 and 7.Experimental and therapeutic medicine · 2021Article
- Article
- Calcium Transport in Specialized Dental Epithelia and Its Modulation by Fluoride.Frontiers in endocrinology · 2021Review
- Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation.Frontiers in pharmacology · 2021Article
- Histone acetyltransferase promotes fluoride toxicity in LS8 cells.Chemosphere · 2020Article
- Principles of fluoride toxicity and the cellular response: a review.Archives of toxicology · 2020Review
- Fluoride exposure alters CaScience signaling · 2020Article
- Nitrate and Phosphate Transporters Rescue Fluoride Toxicity in Yeast.Chemical research in toxicology · 2019Article
- Article
- Article
- A mini review of fluoride-induced apoptotic pathways.Environmental science and pollution research international · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundExposure to excessive amounts of fluoride (F(-)) causes dental fluorosis in susceptible individuals; however, the mechanism of F(-)-induced toxicity is unclear. Previously, we have shown that high-dose F(-) activates the unfolded protein response (UPR) in ameloblasts that are responsible for dental enamel formation. The UPR is a signaling pathway responsible for either alleviating endoplasmic reticulum (ER) stress or for inducing apoptosis of the stressed cells.
objectivesIn this study we determined if low-dose F(-) causes ER stress and activates the UPR, and we also determined whether F(-) interferes with the secretion of proteins from the ER.
methodsWe stably transfected the ameloblast-derived LS8 cell line with secreted alkaline phosphatase (SEAP) and determined activity and localization of SEAP and F(-)-mediated induction of UPR proteins. Also, incisors from mice given drinking water containing various concentrations of F(-) were examined for eucaryotic initiation factor-2, subunit alpha (eIF2alpha) phosphorylation.
resultsWe found that F(-) decreases the extracellular secretion of SEAP in a linear, dose-dependent manner. We also found a corresponding increase in the intracellular accumulation of SEAP after exposure to F(-). These changes are associated with the induction of UPR proteins such as the molecular chaperone BiP and phosphorylation of the UPR sensor PKR-like ER kinase, and its substrate, eIF2alpha. Importantly, F(-)-induced phosphorylation of eIF2alphawas confirmed in vivo.
conclusionsThese data suggest that F(-) initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.