Abstract
Hydrofluoric acid elicits cell cycle arrest through a mechanism that has long been presumed to be linked with the high affinity of fluoride to metals. However, we have recently found that the acid stress from fluoride exposure is sufficient to elicit many of the hallmark phenotypes of fluoride toxicity. Here we report the systematic screening of genes involved in fluoride resistance and general acid resistance using a genome deletion library in Saccharomyces cerevisiae. We compare these to a variety of acids – 2,4-dinitrophenol, FCCP, hydrochloric acid, and sulfuric acid – none of which has a high metal affinity. Pathways involved in endocytosis, vesicle trafficking, pH maintenance, and vacuolar function are of particular importance to fluoride tolerance. The majority of genes conferring resistance to fluoride stress also enhanced resistance to general acid toxicity. Genes whose expression regulate Golgi-mediated vesicle transport were specific to fluoride resistance, and may be linked with fluoride-metal interactions. These results support the notion that acidity is an important and underappreciated principle underlying the mechanisms of fluoride toxicity.
•• The full article is available in pdf (see attachment) and also online at https://www.frontiersin.org/articles/10.3389/fmicb.2020.01410/full
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Fluoride metabolism
Knowledge of all aspects of fluoride metabolism is essential for comprehending the biological effects of this ion in humans as well as to drive the prevention (and treatment) of fluoride toxicity. Several aspects of fluoride metabolism - including gastric absorption, distribution and renal excretion - are pH-dependent because the coefficient
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Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F1 Mice (Drinking Water Studies)
CASRN: 7681-49-4 Chemical Formula: NaF Molecular Weight: 41.99 Report Date: December 1990 Sodium fluoride is a white, crystalline, water-soluble powder used in municipal water fluoridation systems, in various dental products, and in a variety of industrial applications. Toxicology and carcinogenesis studies were conducted with F344/N rats and B6C3F1 mice of each sex by incorporating
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Liver proteome of mice with different genetic susceptibilities to the effects of fluoride
OBJECTIVE: In this study, we investigated the differential pattern of protein expression in the liver of these mice to provide insights on why they have different responses to F. MATERIAL AND METHODS: Weanling male A/J and 129P3/J mice (n=10 from each strain) were pared and housed in metabolic cages with ad
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Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERa gene polymorphisms?
Highlights Adverse effect of fluoride exposure on human beings is a major public issue in China. Fluoride exposure significantly changed the serum level of estradiol in male farmers. Polymorphisms of ERa gene affected serum reproductive hormone levels in male. Gene-environment and gene-gene interactions on reproductive hormones were found. The occurrence of
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Evaluation of genetic polymorphisms in MMP2, MMP9 and MMP20 in Brazilian children with dental fluorosis.
Highlights MMP2, MMP9 and MMP20 were expressed in the enamel development of the animalmodels. Polymorphisms in MMP2, MMP9 and MMP2 were not associated with dental fluorosis. Afro-descendants had a higher risk of dental fluorosis than caucasian. Recent studies suggested that genetics contribute to differences in dental fluorosis (DF) susceptibility among individuals
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