Liver proteome of mice with different genetic susceptibilities to the effects of fluoride

Khan, Zohaib Nisar; Leite, Aline de Lima; Charone, Senda; Sabino, Isabela Tomazini; Martini, Tatiana; Pereira, Heloísa Aparecida Barbosa da Silva; Oliveira, Rodrigo Cardoso de; Buzalaf, Marília Afonso Rabelo

doi:10.1590/1678-775720150364

Cited by 7 publications

(8 citation statements)

References 23 publications

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“…A large majority of the protein changes observed with low-fat feeding (both up-and downregulated) are related to fat and carbohydrate metabolism. This is consistent with previous proteomic assessment of diet-influenced protein profile in livers of both rats (50) and mice (51). Supplement Tables 14 and 15 show protein changes in mice on high-fat diet treated with OCA.…”

Section: Resultssupporting

confidence: 89%

Liver Protein Expression in Nash Mice on a High-Fat Diet

Varani

McClintock

Knibbs

et al. 2022

Preprint

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Male MS-NASH mice were maintained on a high-fat diet for 16 weeks with and without red algae-derived minerals. Obeticholic acid (OCA) was used as a comparator in the same strain and diet. C57BL/6 mice maintained on a standard (low-fat) rodent chow diet were used as a control. At the end of the in-life portion of the study, body weight, liver weight, liver enzyme levels and liver histology were assessed. Samples obtained from individual livers were subjected to Tandem Mass Tag labeling/mass spectroscopy for protein profile determination. As compared to mice maintained on the low-fat diet, all high-fat-fed mice had increased whole body and liver weight, increased liver enzyme (aminotransferases) levels and widespread steatosis/ballooning hepatocyte degeneration. Histological evidence for liver inflammation and collagen deposition was also present, but changes were to a lesser extent. A moderate reduction in ballooning degeneration and collagen deposition was observed with mineral supplementation. Control mice on the high-fat diet alone demonstrated multiple protein changes associated with dysregulated fat and carbohydrate metabolism, lipotoxicity and oxidative stress. Cholesterol metabolism and bile acid formation were especially sensitive to diet. In mice receiving multi-mineral supplementation along with the high-fat diet, there was reduced liver toxicity as evidenced by a decrease in levels of several cytochrome P450 enzymes and other oxidant-generating moieties. Additionally, elevated expression of several keratins was also detected in mineral-supplemented mice. The protein changes observed with mineral supplementation were not seen with OCA. Our previous studies have shown that mice maintained on a high-fat diet for up to 18 months develop end-stage liver injury including hepatocellular carcinoma. Mineral-supplemented mice were substantially protected against tumor formation and other end-state consequences of high-fat feeding. The present study identifies early (16-week) protein changes occurring in the livers of the high-fat diet-fed mice, and how the expression of these proteins is influenced by mineral supplementation. These findings help elucidate early protein changes that contribute to end-stage liver injury and potential mechanisms by which dietary minerals may mitigate such damage.

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Section: Resultssupporting

confidence: 89%

Liver Protein Expression in Nash Mice on a High-Fat Diet

Varani

McClintock

Knibbs

et al. 2022

Preprint

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“…Regarding the proteomic analysis of the liver, S non-exercised mice, especially when drinking deionized water, had an increase in protein expression (Table 4). This is in accordance with a recent study by our group when the liver proteome of these two mice strains was compared and might be explained by an increase in Formimidoyltransferasecyclodeaminase (Q91XD4; Table S1) [32] that was exclusively identified in the S mice in the present study. This enzyme is involved in the synthesis of purines and pyrimidines, as well as amino acids [33].…”

Section: Discussionsupporting

confidence: 94%

“…Increased energy flux leads to oxidative stress, which agrees with an increase in antioxidant enzymes in S mice not exposed to F compared with their R counterparts. These findings were also observed in a previous study of our group [32]. The increase in proteins related to energy flux and antioxidant proteins in S mice might be a plausible explanation for their high susceptibility to the effects of F, since this ion is well known for its ability to induce oxidative stress [3,4,32].…”

Section: Discussionsupporting

confidence: 87%

“…These findings were also observed in a previous study of our group [32]. The increase in proteins related to energy flux and antioxidant proteins in S mice might be a plausible explanation for their high susceptibility to the effects of F, since this ion is well known for its ability to induce oxidative stress [3,4,32].…”

Section: Discussionsupporting

confidence: 87%

“…However, in the presence of two stressors (F and exercise), there is a remarkable reduction in proteins involved in protein synthesis, energy metabolism, and detoxification, but antioxidant enzymes are still increased in the S mice (SIII compared to RIII mice). These results, when analyzed in conjunction with the literature, suggest an increased state of oxidative stress in S mice that is inherent to this strain and might be exacerbated by the treatment with F, which is also known to provoke oxidative stress [3,7,32].…”

Section: Discussionmentioning

confidence: 59%

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Effect of Physical Exercise and Genetic Background on Glucose Homeostasis and Liver/Muscle Proteomes in Mice

et al. 2022

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We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. In R-mice, exercise resulted in an increase in F accumulation in the femur. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise.

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Liver Proteome of Mice with Distinct Genetic Susceptibilities to Fluorosis Treated with Different Concentrations of F in the Drinking Water

Khan

Sabino

Melo

et al. 2018

Biol Trace Elem Res

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Appropriate doses of fluoride (F) have therapeutic action against dental caries, but higher levels can cause disturbances in soft and mineralized tissues. Interestingly, the susceptibility to the toxic effects of F is genetically determined. This study evaluated the effects of F on the liver proteome of mice susceptible (A/J) or resistant (129P3/J) to the effects of F. Weanling male A/J (n = 12) and 129P3/J (n = 12) mice were housed in pairs and assigned to two groups given low-F food and drinking water containing 15 or 50 ppm F for 6 weeks. Liver proteome profiles were examined using nano-LC-ESI-MS/MS. Difference in expression among the groups was determined using the PLGS software. Treatment with the lower F concentration provoked more pronounced alterations in fold change in liver proteins in comparison to the treatment with the higher F concentration. Interestingly, most of the proteins with fold change upon treatment with 15 ppm F were increased in the A/J mice compared with their 129P3/J counterparts, suggesting an attempt of the former to fight the deleterious effects of F. However, upon treatment with 50 ppm F, most proteins with fold change were decreased in the A/J mice compared with their 129P3/J counterparts, especially proteins related to oxidative stress and protein folding, which might be related to the higher susceptibility of the A/J animals to the deleterious effects of F. Our findings add light into the mechanisms underlying genetic susceptibility to fluorosis.

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Liver proteome of mice with different genetic susceptibilities to the effects of fluoride

Cited by 7 publications

References 23 publications

Liver Protein Expression in Nash Mice on a High-Fat Diet

Liver Protein Expression in Nash Mice on a High-Fat Diet

Effect of Physical Exercise and Genetic Background on Glucose Homeostasis and Liver/Muscle Proteomes in Mice

Liver Proteome of Mice with Distinct Genetic Susceptibilities to Fluorosis Treated with Different Concentrations of F in the Drinking Water

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