Proteomic Analysis of Liver in Rats Chronically Exposed to Fluoride

被引:53
作者
Barbosa da Silva Pereira, Heloisa Aparecida [1 ]
Leite, Aline de Lima [1 ]
Charone, Senda [1 ]
Vaz Madureira Lobo, Janete Gualiume [1 ]
Cestari, Tania Mary [1 ]
Peres-Buzalaf, Camila [1 ]
Rabelo Buzalaf, Marilia Afonso [1 ]
机构
[1] Univ Sao Paulo, Dept Biol Sci, Bauru Dent Sch, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
INDUCED APOPTOSIS; SODIUM-FLUORIDE; PROTEINS; STRESS; TRANSLATION; PEROXISOMES; PHOSPHATASE; INHIBITION; METABOLISM; ACTIVATION;
D O I
10.1371/journal.pone.0075343
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fluoride (F) is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old) were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group). At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS). Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE) and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.
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页数:11
相关论文
共 56 条
[1]   Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells [J].
Anuradha, CD ;
Kanno, S ;
Hirano, S .
FREE RADICAL BIOLOGY AND MEDICINE, 2001, 31 (03) :367-373
[2]   Molecular mechanisms of fluoride toxicity [J].
Barbier, Olivier ;
Arreola-Mendoza, Laura ;
Maria Del Razo, Luz .
CHEMICO-BIOLOGICAL INTERACTIONS, 2010, 188 (02) :319-333
[3]   A 2-STEP MECHANISM OF FLUORIDE INHIBITION OF RAT-LIVER INORGANIC PYROPHOSPHATASE [J].
BAYKOV, AA ;
ALEXANDROV, AP ;
SMIRNOVA, IN .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 294 (01) :238-243
[4]   INTERACTIONS OF EUKARYOTIC ELONGATION-FACTOR-2 WITH ACTIN - A POSSIBLE LINK BETWEEN PROTEIN SYNTHETIC MACHINERY AND CYTOSKELETON [J].
BEKTAS, M ;
NURTEN, R ;
GUREL, Z ;
SAYERS, Z ;
BERMEK, E .
FEBS LETTERS, 1994, 356 (01) :89-93
[5]   Apolipoprotein E and its role in aging and survival [J].
Bonomini, Francesca ;
Filippini, Francesca ;
Hayek, Tony ;
Aviram, Michael ;
Keidar, Shlomo ;
Rodella, Luigi F. ;
Coleman, Raymond ;
Rezzani, Rita .
EXPERIMENTAL GERONTOLOGY, 2010, 45 (02) :149-157
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   Blue silver: A very sensitive colloidal Coomassie G-250 staining for proteome analysis [J].
Candiano, G ;
Bruschi, M ;
Musante, L ;
Santucci, L ;
Ghiggeri, GM ;
Carnemolla, B ;
Orecchia, P ;
Zardi, L ;
Righetti, PG .
ELECTROPHORESIS, 2004, 25 (09) :1327-1333
[8]   Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice [J].
Chattopadhyay, Ansuman ;
Podder, Santosh ;
Agarwal, Soumik ;
Bhattacharya, Shelley .
ARCHIVES OF TOXICOLOGY, 2011, 85 (04) :327-335
[9]   Rapid up-regulation of peptide elongation factor EF-1α protein levels is an immediate early event during oxidative stress-induced apoptosis [J].
Chen, E ;
Proestou, G ;
Bourbeau, D ;
Wang, E .
EXPERIMENTAL CELL RESEARCH, 2000, 259 (01) :140-148
[10]  
Cheng TJ, 1998, J CELL BIOCHEM, V69, P221, DOI 10.1002/(SICI)1097-4644(19980501)69:2<221::AID-JCB12>3.0.CO