Proteomics analysis of liver samples from puffer fish Takifugu rubripes exposed to excessive fluoride: An insight into molecular response to fluorosis

Abstract

Comparative proteomics was performed to identify proteins in the liver of Takifugu rubripes in response to excessive fluoride exposure. Sixteen fish were randomly divided into a control group and an experimental group. The control group was raised in soft water alone (F(-) = 0.4 mg/L), and the experimental group was raised in the same water with sodium fluoride at a high concentration of 35 mg/L. After 3 days, proteins were extracted from the fish livers and then subjected to two-dimensional polyacrylamide gel electrophoresis analysis. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to identify the proteins that were differentially expressed from the two groups of fish. Among an average of 816 and 918 proteins detected in the control and treated groups, respectively, 16 proteins were upregulated and 35 were downregulated (P < 0.01) in the fluoride-treated group as compared with those in the control group. Twenty-four highly differentially expressed proteins were further analyzed by MALDI-TOF/TOF-MS, and eight were identified by Mascot. These eight proteins include disulfide isomerase ER-60, 4SNc-Tudor domain protein, SMC3 protein, Cyclin D1, and mitogen-activated protein kinase 10, as well as three unknown proteins. Consistent with their previously known functions, these identified proteins seem to be involved in apoptosis and other functions associated with fluorosis. These results will greatly contribute to our understanding of the effects of fluoride exposure on the physiological and biochemical functions of Takifugu and the toxicological mechanism of fluoride causing fluorosis in both fish and human.

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

“…Thus, gene expression profiling of the sperm cells from fluorideexposed mice has shown that 34 studied genes were upregulated and 63 genes were downregulated, most of which are involved in the signal transduction, amino acid phosphorylation, oxidative stress, cell cycle, electron transfer, glycolysis, chemotaxis, spermatogenesis, and apoptosis [105]. Comparative proteomic analysis of the kidney, liver, and cardiac muscle samples from puffer fish Takifugu rubripes exposed to excessive fluoride has revealed that among a few tens of proteins, found to be either upregulated or downregulated, five or more proteins seem to be involved in apoptosis and other functions associated with fluorosis [141][142][143]. Those are disulfide isomerase ER-60 playing a key role in the degradation of misfolded proteins and refolding of denatured proteins in ER, SMC3, and SMC4 proteins taking part in DNA recombination and repair, as well as chromosome segregation, 4NSc-Tudor domain protein (nuclear factor kappa B2 NF-kB2) which proapoptotic function is stabilization of p53, cyclin D1, a nuclear protein repressed by p53 and required for cell cycle progression, MAPK10 (c-Jun N-terminal kinase 3 JNK3), thought to phosphorylate p53 and playing an important role in nuclear signal transduction associated with apoptosis [144][145][146][147].…”

Ameliorative effect of protein and calcium on fluoride-induced hepatotoxicity in rabbits

“…F ion (mg/kg), protein (Pr) and calcium (Ca) level (%), and energy density (ED, MJ/kg) in the diet of the rabbits. differentially (Lu et al, 2010). In rat liver, enzymes of the antioxidative system, such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), were significantly inhibited after NaF exposure (Blaszczyk et al, 2011).…”