Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride
Joint Authors
Agalakova, Natalia Ivanovna
Gusev, Gennadii Petrovich
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-03-07
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant.
Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects.
The molecular mechanisms underlying fluoride toxicity are different by nature.
Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca2+-, and MAPK-dependent systems.
G-protein-independent routes include tyrosine phosphorylation and protein phosphatase inhibition.
Along with other toxic effects, fluoride was shown to induce oxidative stress leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of cellular ATP and disturbances in cellular metabolism.
Fluoride triggers the disruption of mitochondria outer membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic pathway.
Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be implicated in fluoride-induced apoptosis.
Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2 family proteins and upregulates the expression of p53 protein.
Finally, fluoride changes the expression profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein synthesis.
American Psychological Association (APA)
Agalakova, Natalia Ivanovna& Gusev, Gennadii Petrovich. 2012. Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride. ISRN Cell Biology،Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-469327
Modern Language Association (MLA)
Agalakova, Natalia Ivanovna& Gusev, Gennadii Petrovich. Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride. ISRN Cell Biology No. 2012 (2012), pp.1-16.
https://search.emarefa.net/detail/BIM-469327
American Medical Association (AMA)
Agalakova, Natalia Ivanovna& Gusev, Gennadii Petrovich. Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride. ISRN Cell Biology. 2012. Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-469327
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-469327