High concentration of sodium fluoride in drinking water induce hypertrophy versus atrophy in mouse skeletal muscle via modulation of sarcomeric proteins

Nagendra, Apoorva H; Najar, Mohd Altaf; Bose, Bipasha; Shenoy, Prashanth

doi:10.1016/j.jhazmat.2022.128654

Cited by 10 publications

(4 citation statements)

References 81 publications

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“…In different types of muscle atrophy, muscle protein is rapidly lost due to the suppression of protein synthesis and increased protein degradation rates [ 49 ]. A significant increase in cell proliferation and protein synthesis is seen when the skeletal muscle (mouse) was exposed to NaF (drinking water) for 15 days (80ppm concentration), causing hypertrophy of the muscle, and in the same study, we found a net protein breakdown was observed when the skeletal muscle (mouse) was exposed to NaF (drinking water) for 60 days (80ppm concentration) with an increase in protein degradation [ 50 ]. The increase in protein synthesis following NaF treatment at 15 days might be due to increased translation (mRNA) and transcriptional up-regulation following the treatment.…”

Section: Resultsmentioning

confidence: 93%

“…Further, as the concentration of NaF increases (5ppm), the accumulation of ubiquitinated proteins increases, indicating that proteasome-related proteolysis was enhanced. In our previous study [5,50] we saw an increase in the expression of muscle transcription factor MyoD at the same concentration (1.5ppm; low concentration and early time point) in C2C12 myoblast and C57BL6 mouse muscle was exposed to NaF. This suggests the critical role played by UPS in muscle regeneration.…”

Section: Plos Onementioning

confidence: 80%

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Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

et al. 2022

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Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014.

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Section: Resultsmentioning

confidence: 93%

Section: Plos Onementioning

confidence: 80%

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

et al. 2022

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“…At excessive exposure levels, ingestion of fluoride causes dental fluorosis, skeletal fluorosis and manifestations such as gastrointestinal, neurological and urinary problems [23]. But some authors pay attention to the disturbing symptoms of the muscular system in the case of fluorides exposure [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Fluoride as a Potential Repressor of Glycogen Metabolism in Skeletal Muscle Cell Line CCL136

et al. 2023

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The exposure of humans to fluorine is connected with its presence in the air, food and water. It is well known that fluorides even at a low concentration but with long time exposure accumulate in the body and lead to numerous metabolic disorders. Fluoride is recognised as a factor modulating the energy metabolism of cells. This interaction is of particular importance in muscle cells, which are cells with high metabolic activity related to the metabolism of glucose and glycogen. In someone suffering from chronic fluoride poisoning, frequent symptoms are chronic fatigue not relieved by extra sleep or rest, muscular weakness, muscle spasms, involuntary twitching. The aim of this study was to examine the effect of fluorine at concentrations determined in blood of people environmentally exposed to fluorides on activity and expression of enzymes taking part in metabolism of muscle glycogen. CCL136 cells were cultured under standard conditions with the addition of NaF. The amount of ATP produced by the cells was determined using the HPLC method, the amount and expression of genes responsible for glycogen metabolism using WB and RT PCR methods and the amount of glycogen in cells using the fluorimetric and PAS methods. It has been shown that in CCL136 cells exposed to 1, 3 and 10 μM NaF there is a change in the energy state and expression pattern of enzymes involved in the synthesis and breakdown of glycogen. It was observed that NaF caused a decrease in ATP content in CCL136 cells. Fluoride exposure also increased glycogen deposition. These changes were accompanied by a decrease in gene expression and the level of enzymatic proteins related to glycogen metabolism: glycogen synthase, glycogen synthase kinase and glycogen phosphorylase. The results obtained shed new light on the molecular mechanisms by which fluoride acts as an environmental toxin.

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“…Although transcriptomic studies are one strategy to explore pathological changes in bone cells or tissue, other mechanisms may be better studied by proteomic, epigenomic, and/or metabolomic approaches; eg, processes that involve cellular stress, transcription factor binding, or environmentally induced HBM after exposure to excessive levels of sodium fluoride (skeletal fluorosis). ( 96 ) These less common omic strategies are yet to be conducted widely in bone, but they have great potential.…”

Section: Understanding Hbm Mechanisms Through Functional Genomicsmentioning

confidence: 99%

High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench

Bergen

Maurizi

Formosa

et al. 2020

Journal of Bone and Mineral Research

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Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease-causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics canThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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High concentration of sodium fluoride in drinking water induce hypertrophy versus atrophy in mouse skeletal muscle via modulation of sarcomeric proteins

Cited by 10 publications

References 81 publications

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

Fluoride as a Potential Repressor of Glycogen Metabolism in Skeletal Muscle Cell Line CCL136

High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench

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