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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Effect of sodium fluoride on the sperm mitochondrial DNA in mice.
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Trends of SHBG and ABP levels in male farmers: Influences of environmental fluoride exposure and ESR alpha gene polymorphisms.
A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESR?) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen
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[Qualitative and quantitative variation of serum proteins in fluorosis patients].
Comparison between patients with occupational fluorosis, a group of healthy workers, and a sample from the general population revealed differences in concentrations of some polymorphic serum proteins. These differences depended on phenotypes of patients. TF 1-2, PI 1-2, and HP 2-1 patients exhibited a decreased concentration of transferrin (TF), a
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Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F1 Mice (Drinking Water Studies)
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