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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Investigation on children’s growth and development under long-term fluoride exposure
Objective To study the influence on children’s growth by long-term high fluoride exposure. Methods Case group was selected in high fluoride areas and control group was selected in non-high fluoride areas. The difference of children’s growth levels were analyzed between 2 groups. Results The IQ of case group was significantly lower than that of control
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The spectrum of radiographic bone changes in children with fluorosis
Painful, crippling deformities in Tanzanian children from an area of endemic fluorosis are reported. Excessive fluoride ingestion in pregnant women may possibly poison and alter enzyme and hormonal systems in the fetus causing disturbances to osteoid formation and mineralization. Knock-knees, bowlegs, and saber shins develop when walking begins. Combinations of osteomalacia, osteoporosis,
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Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China.
Highlights Urine fluoride was inversely associated with IQ. IQ of children with high-activity MAOA genotype was lower than IQ of those with low-activity or female heterozygote genotype. DAT1 and MAOA gene polymorphism modify the effects of UF on IQ. UF, ANKK1, COMT and MAOA have a high-dimensional interaction on
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Fluoride pharmacokinetics during acid-base balance changes in man
Five healthy subjects were each given fluoride 3.0 mg (F) as sodium fluoride tablets on two occasions - during production of acid urine, induced by giving NH4Cl, and during production of alkaline urine obtained by giving NaHCO3. Frequent plasma and urine samples were taken up to 12 h and were
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Factors which increase the risk for skeletal fluorosis
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Mayo Clinic: Fluoridation & Bone Disease in Renal Patients
The available evidence suggests that some patients wtih long-term renal failure are being affected by drinking water with as little as 2 ppm fluoride. The finding of adverse effects in patients drinking water with 2 ppm of fluoride suggests that a few similar cases may be found in patients imbibing 1 ppm, especially if large volumes are consumed, or in heavy tea drinkers. The finding of adverse effects in patients drinking water with 2 ppm of fluoride suggests that a few similar cases may be found in patients imbibing 1 ppm, especially if large volumes are consumed, or in heavy tea drinkers and if fluoride is indeed the cause. It would seem prudent, therefore, to monitor the fluoride intake of patients with renal failure living in high fluoride areas.
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Skeletal Fluorosis & Individual Variability
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