Adaptive response of Living Beings to Extreme Environments: Integrative Approaches from Cellular and Molecular Biology, Biotechnology, Microbiology to Physiology

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The changes of ferroptosis-related gene expression in fluoride-resistant MC3T3-E1 cells. (A) Cell-Counting-Kit-8 assay was used to determine the cell proliferation rate. Fluoride-resistant MC3T3-E1 (FR MC3T3-E1) cells, were inducted by sub-cultivating in 10 ppm fluoride concentration gradient ascending media, and continued till the proliferation rate of the cells in the fluoride media became normal. (B) Real-time PCR showed the changes of ferroptosis-related gene expression between 30 ppm FR MC3T3-E1 cells and WT MC3T3-E1 cells. When cultured in 30 ppm fluoride medium, the expression of Prostaglandin-Endoperoxide Synthase 2 (PTGS2) in FR cells was lower than that in WT cells, which is the marker of ferroptosis. Dual Oxidase 1 (DUOX1), Lipin 1 (LIPIN1), Sirtuin 1 (SIRT1), Solute Carrier Family 38 Member 1 (SCL38A1), and Transferrin Receptor (TFRC) are the drivers of ferroptosis. Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2), GPX4, NAD(P)H Quinone Dehydrogenase 1 (NQO1) are ferroptosis suppressors. The result indicates that the expression of ferroptosis driver in FR cells is lower than that in WT cells. Similarly, the expression of ferroptosis suppressor in FR cells was significantly higher than that in WT cells. *p < 0.05; **p < 0.01; ***p < 0.001 and ****p < 0.0001.
Perspective
07 December 2021
Prospects for the Role of Ferroptosis in Fluorosis
Yi Zhang
4 more and 
Bin Liu

As a strong oxidant, fluorine can induce oxidative stress resulting in cellular damage. Ferroptosis is an iron-dependent type of cell death caused by unrestricted lipid peroxidation (LPO) and subsequent plasma membrane rupture. This article indicated a relationship between fluorosis and ferroptosis. Evidence of the depletion of glutathione (GSH) and increased oxidized GSH can be found in a variety of organisms in high fluorine environments. Studies have shown that high fluoride levels can reduce the antioxidant capacity of antioxidant enzymes, while increasing the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in oxidative stress and fluoride-induced oxidative stress, which are related to iron metabolism disorders. Excessive fluorine causes insufficient GSH, glutathione peroxidase (GSH-Px) inhibition, and oxidative stress, resulting in ferroptosis, which may play an important role in the occurrence and development of fluorosis.

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