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Zhi-zhong Guan - One of the best experts on this subject based on the ideXlab platform.
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Decreased nicotinic receptors in PC12 cells and rat brains influenced by Fluoride Toxicity--a mechanism relating to a damage at the level in post-transcription of the receptor genes.
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1-100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR alpha3, alpha7, beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR alpha3 and alpha7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
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decreased nicotinic receptors in pc12 cells and rat brains influenced by Fluoride Toxicity a mechanism relating to a damage at the level in post transcription of the receptor genes
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:Abstract In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1–100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR α3, α7, β2 subunits in PC12 cells, and α4, α7, β2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR α3 and α7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
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Decreased nicotinic receptors in PC12 cells and rat brains influenced by Fluoride Toxicity—a mechanism relating to a damage at the level in post-transcription of the receptor genes
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:Abstract In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1–100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR α3, α7, β2 subunits in PC12 cells, and α4, α7, β2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR α3 and α7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
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Chronic Fluoride Toxicity decreases the number of nicotinic acetylcholine receptors in rat brain
Neurotoxicology and teratology, 2002Co-Authors: Yi-guo Long, Agneta Nordberg, Ya-nan Wang, Jia Chen, Su-fen Jiang, Zhi-zhong GuanAbstract:Abstract In order to investigate the molecular mechanism(s) underlying brain dysfunction caused by chronic fluorosis, neuronal nicotinic acetylcholine receptors (nAChRs) in the brain of rats receiving either 30 or 100 ppm Fluoride in their drinking water for 7 months were analyzed in the present study employing ligand binding and Western blotting. There was a significant reduction in the number of [ 3 H]epibatidine binding sites in the brain of rats exposed 100 ppm of Fluoride, but no alteration after exposed to 30 ppm. On the other hand, the number of [ 125 I]α-BTX binding sites was significantly decreased in the brains of rats exposed to both levels of Fluoride. Western blotting revealed that the level of the nAChR α4 subunit protein in the brains of rats was significantly lowered by exposure to 100 ppm, but not 30 ppm Fluoride; whereas the expression of the α7 subunit protein was significantly decreased by both levels of exposure. In contrast, there was no significant change in the level of the β2 subunit protein in the brains of rats administered Fluoride. Since nAChRs play major roles in cognitive processes such as learning and memory, the decrease in the number of nAChRs caused by Fluoride Toxicity may be an important factor in the mechanism of brain dysfunction in the disorder.
Scott A. Strobel - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Identification of Genes Involved in General Acid Stress and Fluoride Toxicity in Saccharomyces cerevisiae.
Frontiers in microbiology, 2020Co-Authors: Nichole R. Johnston, Sunitha Nallur, Patricia B. Gordon, Kathryn D. Smith, Scott A. StrobelAbstract: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.
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Principles of Fluoride Toxicity and the cellular response: a review
Archives of Toxicology, 2020Co-Authors: Nichole R. Johnston, Scott A. StrobelAbstract:Fluoride is ubiquitously present throughout the world. It is released from minerals, magmatic gas, and industrial processing, and travels in the atmosphere and water. Exposure to low concentrations of Fluoride increases overall oral health. Consequently, many countries add Fluoride to their public water supply at 0.7–1.5 ppm. Exposure to high concentrations of Fluoride, such as in a laboratory setting often exceeding 100 ppm, results in a wide array of Toxicity phenotypes. This includes oxidative stress, organelle damage, and apoptosis in single cells, and skeletal and soft tissue damage in multicellular organisms. The mechanism of Fluoride Toxicity can be broadly attributed to four mechanisms: inhibition of proteins, organelle disruption, altered pH, and electrolyte imbalance. Recently, there has been renewed concern in the public sector as to whether Fluoride is safe at the current exposure levels. In this review, we will focus on the impact of Fluoride at the chemical, cellular, and multisystem level, as well as how organisms defend against Fluoride. We also address public concerns about Fluoride Toxicity, including whether Fluoride has a significant effect on neurodegeneration, diabetes, and the endocrine system.
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Nitrate and Phosphate Transporters Rescue Fluoride Toxicity in Yeast.
Chemical research in toxicology, 2019Co-Authors: Nichole R. Johnston, Scott A. StrobelAbstract:Organisms are exposed to Fluoride in the air, water, and soil. Yeast and other microbes utilize Fluoride channels as a method to prevent intracellular Fluoride accumulation and mediate Fluoride Toxicity. Consequently, deletion of Fluoride exporter genes (FEX) in S. cerevisiae resulted in over 1000-fold increased Fluoride sensitivity. We used this FEX knockout strain to identify genes, that when overexpressed, are able to partially relieve the Toxicity of Fluoride exposure. Overexpression of five genes, SSU1, YHB1, IPP1, PHO87, and PHO90, increase Fluoride tolerance by 2- to 10-fold. Overexpression of these genes did not provide improved Fluoride resistance in wild-type yeast, suggesting that the mechanism is specific to low Fluoride Toxicity in yeast. Ssu1p and Yhb1p both function in nitrosative stress response, which is induced upon Fluoride exposure along with metal influx. Ipp1p, Pho87p, and Pho90p increase intracellular orthophosphate. Consistent with this observation, Fluoride Toxicity is also partia...
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Eukaryotic resistance to Fluoride Toxicity mediated by a widespread family of Fluoride export proteins
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Kathryn D. Smith, Ronald R. Breaker, Patricia B. Gordon, Jared H. Davis, Scott A. StrobelAbstract:Fluorine is an abundant element and is toxic to organisms from bacteria to humans, but the mechanisms by which eukaryotes resist Fluoride Toxicity are unknown. The Escherichia coli gene crcB was recently shown to be regulated by a Fluoride-responsive riboswitch, implicating it in Fluoride response. There are >8,000 crcB homologs across all domains of life, indicating that it has an important role in biology. Here we demonstrate that eukaryotic homologs [renamed FEX (Fluoride exporter)] function in Fluoride export. FEX KOs in three eukaryotic model organisms, Neurospora crassa, Saccharomyces cerevisiae, and Candida albicans, are highly sensitized to Fluoride (>200-fold) but not to other halides. Some of these KO strains are unable to grow in Fluoride concentrations found in tap water. Using the radioactive isotope of Fluoride, 18F, we developed an assay to measure the intracellular Fluoride concentration and show that the FEX deletion strains accumulate Fluoride in excess of the external concentration, providing direct evidence of FEX function in Fluoride efflux. In addition, they are more sensitive to lower pH in the presence of Fluoride. These results demonstrate that eukaryotic FEX genes encode a previously unrecognized class of Fluoride exporter necessary for survival in standard environmental conditions.
A. K. Susheela - One of the best experts on this subject based on the ideXlab platform.
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Ultrastructural Studies on the Leydig Cells of Rabbits Exposed to Chronic Fluoride Toxicity
1997Co-Authors: A. K. Susheela, Arbind KumarAbstract:The present communication addresses the effect of chronic Fluoride Toxicity on the structure of rabbit Leydig cells usi ng li ght, scanning and transmission electron microscopy. An ion-specific electrode method was used for the determinati on of Fluoride .in sera. The levels of Fluoride in the sera of Fluoride exposed rabbits were significantly increased (p
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Effects of chronic Fluoride Toxicity on the morphology of ductus epididymis and the maturation of spermatozoa of rabbit.
International journal of experimental pathology, 1995Co-Authors: Arbind Kumar, A. K. SusheelaAbstract:This study used light and scanning electron microscopy to observe the effect of chronic Fluoride Toxicity on the structure of the ductus epididymis, testis and spermatozoa in rabbit. The rabbits were treated with 10 mg NaF/kg body weight/day for 20 and 23 months. Serum Fluoride was estimated by the Fluoride ion-specific electrode method. Fluoride levels in the sera of both 20 and 23-month treated rabbits were significantly increased (P < 0.001). Loss of stereocilia, significant decrease (P < 0.001) in the height of the pseudostratified columnar epithelium and significant increase (P < 0.001) in the diameter of both the caput and cauda ductus epididymis were observed only in the 23-month Fluoride treated rabbits. The decreases in the epithelial cell height (P < 0.01) and the tubular diameter (P < 0.001) of the testis were significant only in 23-month treated animals. Spermatozoa in the lumen of the testis of both treated groups of animals and in the caput and cauda ductus epididymis of 20-month treated animals appeared normal, but spermatozoa in the caput and cauda ductus epididymis of 23-month treated animals were fragmented. In the 23-month Fluoride treated rabbits, the weights of the caput and cauda epididymis were significantly reduced (P < 0.025) and there was also a reduction in the number of secretory granules in these organs. The structural changes observed in the caput and cauda ductus epididymis might adversely affect the maturation of spermatozoa.
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Fluoride Toxicity : a biochemical and scanning electron microscopic study of enamel surface of rabbit teeth
Archives of toxicology, 1993Co-Authors: A. K. Susheela, M. BhatnagarAbstract:The present study has been carried out to investigate the effect of Fluoride Toxicity on the morphology as well as inorganic chemical constituents of rabbit teeth. Rabbits were administered sodium Fluoride at a dose of 10 mg NaF/kg body weight every 24 h for 18 and 23 months. The incisor and molar teeth (whole tooth) were investigated for Fluoride, calcium and phosphorus content in 18- and 23-month treated animals. The enamel surfaces of incisor teeth of 23-month treated animals were examined under scanning electron microscope. A significant increase in Fluoride levels and significant decrease in calcium content was found following Fluoride administration for 18 and 23 months as compared to control. Ca/P ratio was significantly increased only in 23-month treated animals. The scanning electron micrographs revealed hypoplastic, rough, uneven, pitted and cracked enamel surfaces covered with granular deposits as a result of excessive intake of Fluoride. It can be concluded that long term Fluoride administration leads to severe structural alterations on the enamel surface, possibly through defective mineralization.
M. Bhatnagar - One of the best experts on this subject based on the ideXlab platform.
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Fluoride Toxicity : a biochemical and scanning electron microscopic study of enamel surface of rabbit teeth
Archives of toxicology, 1993Co-Authors: A. K. Susheela, M. BhatnagarAbstract:The present study has been carried out to investigate the effect of Fluoride Toxicity on the morphology as well as inorganic chemical constituents of rabbit teeth. Rabbits were administered sodium Fluoride at a dose of 10 mg NaF/kg body weight every 24 h for 18 and 23 months. The incisor and molar teeth (whole tooth) were investigated for Fluoride, calcium and phosphorus content in 18- and 23-month treated animals. The enamel surfaces of incisor teeth of 23-month treated animals were examined under scanning electron microscope. A significant increase in Fluoride levels and significant decrease in calcium content was found following Fluoride administration for 18 and 23 months as compared to control. Ca/P ratio was significantly increased only in 23-month treated animals. The scanning electron micrographs revealed hypoplastic, rough, uneven, pitted and cracked enamel surfaces covered with granular deposits as a result of excessive intake of Fluoride. It can be concluded that long term Fluoride administration leads to severe structural alterations on the enamel surface, possibly through defective mineralization.
Ke-ren Shan - One of the best experts on this subject based on the ideXlab platform.
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Decreased nicotinic receptors in PC12 cells and rat brains influenced by Fluoride Toxicity--a mechanism relating to a damage at the level in post-transcription of the receptor genes.
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1-100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR alpha3, alpha7, beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR alpha3 and alpha7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
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decreased nicotinic receptors in pc12 cells and rat brains influenced by Fluoride Toxicity a mechanism relating to a damage at the level in post transcription of the receptor genes
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:Abstract In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1–100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR α3, α7, β2 subunits in PC12 cells, and α4, α7, β2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR α3 and α7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
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Decreased nicotinic receptors in PC12 cells and rat brains influenced by Fluoride Toxicity—a mechanism relating to a damage at the level in post-transcription of the receptor genes
Toxicology, 2004Co-Authors: Ke-ren Shan, Yi-guo Long, Agneta Nordberg, Zhi-zhong GuanAbstract:Abstract In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from Fluoride Toxicity, we treated PC12 cells by different concentrations of Fluoride (0.1–100 ppm) for 48 h, and exposed rats to high doses of Fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neuroToxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR α3, α7, β2 subunits in PC12 cells, and α4, α7, β2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of Fluoride or rat brains with chronic fluorosis. The decreases of nAChR α3 and α7 subunit proteins in PC12 cells resulted from Fluoride Toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by Fluoride Toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.