ArticleChemosphere2020
Histone acetyltransferase promotes fluoride toxicity in LS8 cells.
Article in Chemosphere, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 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
- Quantification of Fluoride in Serum, Bone, and Teeth in a Murine Model Using Hexamethyldisiloxane-Facilitated Diffusion and Ion-Selective Electrode Measurements.Journal of visualized experiments : JoVE · 2026Article
- Developmental vulnerability to fluoride toxicity: enamel and clearance differences in adolescent versus mature mice.Archives of toxicology · 2026Article
- Management strategies for fluoride toxicity and the critical role of epigenetic therapy.Molecular biology reports · 2025Review
- KMT2D Regulates Tooth Enamel Development.Journal of dental research · 2025Article
- Article
- KMT2D regulates tooth enamel development.bioRxiv : the preprint server for biology · 2024Article
- Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells.International journal of molecular sciences · 2024Article
- Perfluorooctanoic acid-induced cell death via the dual roles of ROS-MAPK/ERK signaling in ameloblast-lineage cells.Ecotoxicology and environmental safety · 2023Article
- Advances in epidemiological status and pathogenesis of dental fluorosis.Frontiers in cell and developmental biology · 2023Review
- Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses.Journal of applied oral science : revista FOB · 2023Article
- Investigation of the anti-pseudorabies virus activity of interferon lambda 3 in cultured porcine kidney epithelial cells.Veterinary medicine and science · 2022Article
- Impacts of Fluoride Neurotoxicity and Mitochondrial Dysfunction on Cognition and Mental Health: A Literature Review.International journal of environmental research and public health · 2021Review
- Curcumin suppresses cell growth and attenuates fluoride-mediated Caspase-3 activation in ameloblast-like LS8 cells.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction.Journal of the American Chemical Society · 2021Article
- Small-Molecule Inhibitors Overcome Epigenetic Reprogramming for Cancer Therapy.Frontiers in pharmacology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Previously we demonstrated that fluoride increased acetylated-p53 (Ac-p53) in LS8 cells that are derived from mouse enamel organ epithelia and in rodent ameloblasts. However, how p53 is acetylated by fluoride and how the p53 upstream molecular pathway responds to fluoride is not well characterized. Here we demonstrate that fluoride activates histone acetyltransferases (HATs) including CBP, p300, PCAF and Tip60 to acetylate p53. HAT activity is regulated by post-translational modifications such as acetylation and phosphorylation. HAT proteins and their post-translational modifications (p300, Acetyl-p300, CBP, Acetyl-CBP, Tip60 and phospho-Tip60) were analyzed by Western blots. p53-HAT binding was detected by co-immunoprecipitation (co-IP). Cell growth inhibition was analyzed by MTT assays. LS8 cells were treated with NaF with/without HAT inhibitors MG149 (Tip60 inhibitor) and Anacardic Acid (AA; inhibits p300/CBP and PCAF). MG149 or AA was added 1 h prior to NaF treatment. Co-IP results showed that NaF increased p53-CBP binding and p53-PCAF binding. NaF increased active Acetyl-p300, Acetyl-CBP and phospho-Tip60 levels, suggesting that fluoride activates these HATs. Fluoride-induced phospho-Tip60 was decreased by MG149. MG149 or AA treatment reversed fluoride-induced cell growth inhibition at 24 h. MG149 or AA treatment decreased fluoride-induced p53 acetylation to inhibit caspase-3 cleavage, DNA damage marker γH2AX expression and cytochrome-c release into the cytosol. These results suggest that acetylation of p53 by HATs contributes, at least in part, to fluoride-induced toxicity in LS8 cells via cell growth inhibition, apoptosis, DNA damage and mitochondrial damage. Modulation of HAT activity may, therefore, be a potential therapeutic target to mitigate fluoride toxicity in ameloblasts.
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Registered trials
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