Elevated levels of eukaryotic initiation factor 4E (eIF4E) are implicated in neoplasia, with cumulative evidence pointing to its role in the etiopathogenesis of hematological diseases. As a node of convergence for several oncogenic signaling pathways, eIF4E has attracted a great deal of interest from biologists and clinicians whose efforts have been targeting this translation factor and its biological circuits in the battle against leukemia. The role of eIF4E in myeloid leukemia has been ascertained and drugs targeting its functions have found their place in clinical trials. Little is known, however, about the pertinence of eIF4E to the biology of lymphocytic leukemia and a paucity of literature is available in this regard that prospectively evaluates the topic to guide practice in hematological cancer. A comprehensive analysis on the significance of eIF4E translation factor in the clinical picture of leukemia arises, therefore, as a compelling need. This review presents aspects of eIF4E involvement in the realm of the lymphoblastic leukemia status; translational control of immunological function via eIF4E and the state-of-the-art in drugs will also be outlined., V. Venturi, T. Masek, M. Pospisek., and Obsahuje bibliografii
This study aimed to examine the effect of eicosapentaenoic acid (EPA) on skeletal muscle hypertrophy induced by muscle overload and the associated intracellular signaling pathways. Male C57BL/6J mice were randomly assigned to oral treatment with either EPA or corn oil for 6 weeks. After 4 weeks of treatment, the gastrocnemius muscle of the right hindlimb was surgically removed to overload the plantaris and soleus muscles for 1 or 2 weeks. We examined the effect of EPA on the signaling pathway associated with protein synthesis using the soleus muscles. According to our analysis of the compensatory muscle growth, EPA administration enhanced hypertrophy of the soleus muscle but not hypertrophy of the plantaris muscle. Nevertheless, EPA administration did not enhance the expression or phosphorylation of Akt, mechanistic target of rapamycin (mTOR), or S6 kinase (S6K) in the soleus muscle. In conclusion, EPA enhances skeletal muscle hypertrophy, which can be independent of changes in the AKT-mTOR-S6K pathway.
Genetic strain-dependent reactivity to mechanical stimuli in rat skeletal muscle has not been examined. This study aimed to examine whether genetic strain-dependency is associated with reactivity in protein metabolism and the resultant muscle hypertrophy after isometric resistance training (RT). The right triceps of Sprague-Dawley (SD) and Wistar rats underwent 12 sessions of RT. After RT, a transition from the IIb to the IIx myosin heavy-chain isoform was observed in both strains. In SD rats, the lateral gastrocnemius muscle (LG) mass of the trained legs (TRN) was significantly higher than that of the control legs (CON) (7.8 %, P<0.05). Meanwhile, in Wistar rats, the LG mass was unchanged. In SD rats, the levels of 70-kDa ribosomal protein S6 kinase (p70S6k) and forkhead box 3a (FOXO3a) phosphorylation in the TRN were significantly greater than those of the CON (2.2- and 1.9-fold, respectively; P<0.05). The expression of muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) in the TRN were significantly lower than those of the CON (0.6- and 0.7-fold, respectively; P<0.05). However, in Wistar rats, there was no significant difference. These results suggest a genetic strain difference in protein metabolism. This phenomenon may be useful for studying individual differences in response to RT., K. Kobayashi ... [et al.]., and Obsahuje seznam literatury
The aim of this work was to study the effects of low energy parenteral diets with different lipid/glucose ratios on rat liver and jejunal mucosa protein synthesis. The studied diets were: LO (100 % glucose, control diet), L25 (25 % lipids: 75 % glucose), L50 (50 % lipids: 50 % glucose) and L75 (75 % lipids: 25 % glucose). All diets were isoenergetic and isonitrogenated, with a standard amino acid content. The diets were assayed in 93 rats with open femoral fracture immobilized by Kirschner pin insertion. The diets were administered for 4 days. On the fifth day, liver and jejunal mucosa protein synthesis were determined. Highest liver protein synthesis rates were obtained with the diet compositions: lipid/carbohydrate ratio: 25 % lipids and 75 % carbohydrates (expressed as energy ratio). A higher proportion of lipids significantly decreases liver protein synthesis (p<0.05). Jejunal mucosa protein synthesis followed the same pattern, with the same statistical differences.
We have studied the effects of hypocaloric diets with different supplements on liver and jejunal mucosa protein synthesis. The supplements assayed were medium chain triglycerides (diet MCT, with 50 % carbohydrates: 25 % long chain triglycerides (LCT): 25 % medium chain triglycerides (MCT), standard amino acids), branched-chain amino acids (diet BCA, identical to control diet L50, with 15.3 % of nitrogen replaced by branched-chain amino acids) and glutamine (diet GLN, identical to diet L50, with 15.3 % of nitrogen replaced by glutamine). The control diet (L50) had 50 % carbohydrates: 50 % LCT and standard amino acids. The diets were assayed on 86 rats with femoral fracture immobilized by Kirschner pin insertion. Nutrition was administered for 4 days. On the fifth day, liver and jejunal mucosa protein synthesis was determined. A branched-chain amino acid supply in a proportion higher than 21.2 % of amino acid nitrogen significantly decreased liver and jejunal mucosa protein synthesis, while the same amount of glutamine did not modify it. MCT had no effect on jejunal mucosa protein synthesis, while it was decreased significantly in the liver.
Male weaning rats were put on a diet with a physiological nutrient combination adjusted for age, milk casein (E7N = 0.79) and wheat gluten (E/M = 0.30) being the sources of protein. The net protein ratio (NPR) was evaluated weekly until 140 days of age. On days 70 and 140, L-((J-14C)-tyrosine was administered intraperitoneally and 12 h later specific tyrosine activity was determined in the protein fraction of liver and muscle by measuring the incorporation of the labeled amino acid in order to assess protein synthesis over the corresponding time period. Regression lines describing the relationship between animals' weight, age and protein source suggested that the daily weight increase was 6.99 g between days 30-77, 2.97 g between days 77-105 and 0.64 g between days 105-140. Muscle tyrosine levels in rapidly growing animals aged 70 days were 91.0 /¿g/g/12 h for casein and 65.6/ig/g/12 h for gluten. Liver tyrosine levels were 336.4 and 189.6 /rg/g/12 h, respectively. The differences observed at this age were highly significant. In adult animals (140 days old) there were non-significant differences between tyrosine levels in the casein- and gluten-fed groups. The isotope study clearly showed that protein synthesis was reduced in growing and developing animals on vegetable nutrition, which is deficient in essential amino acids, (especially the limiting amino acid lysine, crucial for the utilization of all other amino acids in peptide chain synthesis). The low rate of amino acid utilization found in animals younger than 105 days is consistent with the findings obtained by the isotope method.