ABSTRACT
Leucine (Leu) plays a critical regulatory role in protein synthesis, however, the effects and molecular mechanisms of Leu on crop milk protein in the domestic pigeons (Columba livia) are still unknown. Therefore, the study aimed to investigate the effects of dietary Leu supplementation on crop milk protein synthesis and the growth performance of squabs and the possible underlying mechanism. A total of 240 pairs of breeding pigeons (1102.3 ± 9.5 g/pair) were randomly assigned to 1 of 5 treatments, including a positive control (PC) diet that had adequate crude protein (crude protein, CP = 18%; Leu = 1.30%), a negative control (NC) diet that was low in CP (CP = 16%, Leu = 1.30%), and NC diets supplemented with Leu at 0.15%, 0.45%, or 1.05%. Compared with the NC diet, 0.15 to 0.45% Leu supplementation decreased BW loss and increased relative crop weight, crop thickness, and protein levels in the crop tissue and milk of breeding pigeons. However, dietary supplementation with 1.05% Leu inhibited ADFI in breeding pigeons. Dietary supplementation with 0.15 to 0.45% Leu decreased the mortality rate and increased the BW, eviscerated yield, and breast muscle yield of young squabs. The protein expression levels of the target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1), ribosomal protein S6 kinase (S6), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and eukaryotic translation initiation factor 4E (eIF4E) were upregulated in the crop tissue of breeding pigeons in PC, 0.15% and 0.45% Leu-supplemented groups. Collectively, these results indicated that 0.15 to 0.45% Leu supplementation could decrease BW loss, increase milk protein synthesis in the crop of breeding pigeons, and enhance the survival rate and growth performance of young squabs through the TOR signaling pathway.
Subject(s)
Avian Proteins/biosynthesis , Columbidae/metabolism , Crop, Avian/physiology , Leucine/metabolism , Animal Feed/analysis , Animals , Columbidae/growth & development , Diet/veterinary , Dietary Supplements/analysis , Female , Leucine/administration & dosage , Male , Signal TransductionABSTRACT
The objective of this study was to investigate the effects of L-glutamate (Glu) deficiency or L-trans pyrrolidine-2,4-dicarboxylic acid (PDC) supplementation on the proliferation of pig intestinal epithelial cells (IPEC-1). First, IPEC-1 cells were cultured in normal growing medium supplemented with 0 (Control), 50, 100, or 200 µmol/L PDC to determine an appropriate concentration of PDC supplementation. Second, IPEC-1 cells were cultured in Glu-deficient medium supplemented with 0 µmol/L Glu (Glu deficiency), 50 µmol/L Glu (Control), or 50 µmol/L Glu plus 100 µmol/L PDC (PDC supplementation). Cell proliferation ( = 24), cell cycle distribution ( = 6), cell apoptosis ( = 6), and expression levels of proteins of interest ( = 4) were determined by MTT assay, flow cytometry, or western blot. The results showed that cell proliferation was inhibited ( < 0.05) by 50, 100, and 200 µmol/L PDC supplementation at 24 and 48 h after treatment. Variance analysis was performed using the GLM procedure, and the results demonstrated that Glu deficiency or PDC supplementation led to the inhibition ( < 0.05) of cell proliferation, a greater ( < 0.05) percentage of cells in the G1 phase, and a lower ( < 0.05) percentage of cells in the S phase. Moreover, Glu deficiency or PDC supplementation reduced ( < 0.05) the expression levels of excitatory AA transporter 3 (EAAT3), phosphor-mammalian target of rapamycin (p-mTOR; Ser2448), p-ribosomal protein S6 kinase 1 (S6K1; Thr389), and p-S6 (Ser235/236). This study demonstrates that Glu deficiency or PDC supplementation inhibits proliferation of IPEC-1 cells via downregulation of the mTOR/S6K1 pathway and EAAT3 expression indicating that Glu deficiency may lead to the disturbances of intestinal epithelial renewal in pigs, particularly in neonates.
Subject(s)
Cell Proliferation/physiology , Epithelial Cells/drug effects , Glutamic Acid/deficiency , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Swine , TOR Serine-Threonine Kinases/metabolism , Animals , Apoptosis/drug effects , Cell Cycle , Cell Proliferation/drug effects , Dicarboxylic Acids/administration & dosage , Dicarboxylic Acids/pharmacology , Down-Regulation , Epithelial Cells/physiology , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Glutamic Acid/pharmacology , Intestines/drug effects , Pyrrolidines/administration & dosage , Pyrrolidines/pharmacology , Ribosomal Protein S6 Kinases, 70-kDa/genetics , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/geneticsABSTRACT
Glutamate, which is one of the most important contributors to oxidative metabolism in the intestinal mucosa, is mainly transported by the excitatory amino acids transporters (EAATs) that are expressed in enterocytes. The objective of this study was to evaluate the effects of in ovo administration of l-trans pyrrolidine-2,4-dicarboxylic acid (l-trans-PDC), a potent competitive inhibitor of glutamate uptake by EAATs, on the growth of the small intestine in chicks. Two series of experiments were conducted with hatching eggs; 100 µl of various l-trans-PDC solutions (0, 0.075 or 0.225 mg/egg for the Control group, low-dose l-trans pyrrolidine 2,4-dicarboxylic acid group (L-PDC) or high-dose l-trans pyrrolidine 2,4-dicarboxylic acid group (H-PDC), respectively) was injected into the albumen sac of these hatching eggs before incubation. Hatchlings were sacrificed by cervical dislocation to determine the embryonic development in Experiment I, whereas the birds in Experiment II were raised or sampled at hatching, days 7 and 14 (D7 and D14) for further study. Gene expression in the small intestines was determined by real-time RT-PCR; and serum concentration of free amino acids was determined by an amino acid analyzer. The results showed that the hatchability was decreased by in ovo administration of l-trans-PDC. The small intestinal weights of the H-PDC group were decreased (P<0.05) at hatching and increased (P<0.05) on D7 and D14 compared with those in the Control group. In addition, the gene expression of EAAT2 in the completed or segmental small intestines was not changed (P>0.05); EAAT3 gene expression in the duodenum (P<0.05), jejunum (P=0.084) and ileum (P=0.060) on D14 was lower in the H-PDC group than in the Control group. Furthermore, the serum concentrations of free proline, threonine and phenylalanine but not glutamate or aspartate were increased (P<0.06) in H-PDC group. In conclusion, this paper is the first to report that in ovo administration of l-trans-PDC induces small intestinal growth retardation during the embryonic period and catch-up growth after hatching.
Subject(s)
Chick Embryo/drug effects , Chickens/growth & development , Dicarboxylic Acids/administration & dosage , Excitatory Amino Acid Antagonists/administration & dosage , Gene Expression Regulation, Developmental/drug effects , Glutamic Acid/metabolism , Pyrrolidines/administration & dosage , Animals , Body Weight , Chick Embryo/embryology , Chick Embryo/growth & development , Chickens/genetics , Chickens/metabolism , Diet/veterinary , Intestine, Small/drug effects , Intestine, Small/embryology , Intestine, Small/growth & development , Organ SizeABSTRACT
Major depression is a common mood disorder that affects overall health; currently, almost all of the available antidepressants have the same core mechanisms of action through promotion of serotonin or noradrenaline function in the brain. The major limitation of today's antidepressants is that chronic treatment (3 - 6 weeks) is required before a therapeutic benefit is achieved. More effective and faster treatments for depression are needed. Adult neurogenesis is the birth of new neurons, which continues postnatally and into adulthood in the brains of multiple species, including humans. Recently, a large body of evidence gives rise to the hypothesis that the antidepressant effect and increases in adult hippocampal neurogenesis may be causally related. Multiple classes of antidepressants increase hippocampal neurogenesis in a chronic, but not acute, time course. This effect corresponds to the therapeutic time lag associated with current antidepressants. In addition, antidepressants are not effective in behavioral models of depression when hippocampal neurogenesis is prevented. This review examines the current understanding of adult neurogenesis and the evidence of the causal relationship between antidepressant effects and adult hippocampal neurogenesis. We also present our recent research findings, which support a promising strategy for enhancing adult hippocampal neurogenesis that might be a new approach for the development of novel antidepressants.
Subject(s)
Antidepressive Agents/pharmacology , Drug Evaluation, Preclinical , Hippocampus/drug effects , Neurogenesis , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Dentate Gyrus/cytology , Dentate Gyrus/drug effects , Dentate Gyrus/metabolism , Hippocampus/cytology , Hippocampus/metabolism , Humans , Neurogenesis/drug effects , Vascular Endothelial Growth Factor A/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a membrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. Analysis of PECAM-1 expression in the developing mouse embryo has revealed the presence of multiple isoforms of murine PECAM-1 (muPECAM-1) that appeared to result from the alternative splicing of exons encoding cytoplasmic domain sequences (exons 10-16) (Baldwin, H. S., Shen, H. M., Yan, H., DeLisser, H. M., Chung, A., Mickanin, C., Trask, T., Kirschbaum, N. E. Newman, P. J., Albelda, S., and Buck, C. A. (1994) Development 120, 2539-2553). To investigate the functional consequences of alternatively spliced muPECAM-1 cytoplasmic domains, L-cells were transfected with cDNA for each variant and their ability to promote cell aggregation was compared. In this assay, full-length muPECAM-1 and all three isoforms containing exon 14 behaved like human PECAM-1 in that they mediated calcium- and heparin-dependent heterophilic aggregation. In contrast, three muPECAM-1 variants, all missing exon 14, mediated calcium- and heparin-independent homophilic aggregation. Exon 14 thus appears to modulate the ligand and adhesive interactions of the extracellular domain of PECAM-1. These findings suggest that alternative splicing may represent a mode of regulating the adhesive function of PECAM-1 in vivo and provides direct evidence that alternative splicing involving the cytoplasmic domain affects the ligand specificity and binding properties of a cell adhesion receptor.
Subject(s)
Alternative Splicing , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Amino Acid Sequence , Animals , Antibodies, Monoclonal , Antigens, Differentiation, Myelomonocytic/immunology , Base Sequence , Blood Platelets/metabolism , Cell Adhesion Molecules/immunology , Cell Aggregation , Cloning, Molecular , Cytoplasm/metabolism , DNA Primers/genetics , DNA, Complementary/genetics , Embryo, Mammalian , Endothelium, Vascular/metabolism , Exons , Genetic Variation , Glycosylation , Humans , L Cells , Ligands , Mice , Molecular Sequence Data , Platelet Endothelial Cell Adhesion Molecule-1 , Protein Binding , Sequence Deletion , Sequence Homology, Nucleic Acid , TransfectionABSTRACT
The present study investigates the prevalence and type of anaemia in Chinese female cotton mill workers. The prevalence of anaemia is reported in 447 non-pregnant female workers aged between 19 and 45 years. The mean value for haemoglobin (Hb) was 123 (SD 15) g/l and 150 of the total 447 subjects had Hb values below 120 g/l; thus 34% of the population was anaemic according to World Health Organization (WHO, 1975) criteria. The mean value for free erythrocyte protoporphyrin (FEP) was 419 (SD 215) micrograms/l; 55% of the total population had FEP values higher than 350 micrograms/l and 72% among the anaemic subjects. Serum ferritin (SF) was tested in all the women with a Hb value less than 120 g/l and 71% of them had SF values below 12.0 micrograms/l. Eighty women diagnosed as either Fe deficient or with Fe-deficient anaemia were selected for a diagnostic supplementation trial. They were randomly assigned to FeSO4 (60 or 120 mg Fe/d) or placebo treatment for 12 weeks. Fe supplementation increased mean Hb values from 114 to 127 g/l (P < 0.001) and SF levels from 9.7 to 30.0 micrograms/l (P < 0.001), and decreased mean FEP values from 570 to 277 micrograms/l (P < 0.001). The response rate of Hb in the whole Fe-treated group or Fe-treated subjects with an Hb level less than 120 g/l was 90% or 92% respectively. These findings indicate that the type of anaemia in this population was mainly Fe deficiency. It was also found that in this population the severity of anaemia, not the prevalence, was significantly related to the use of intra-uterine devices (IUD).
Subject(s)
Anemia, Hypochromic/epidemiology , Occupational Diseases/epidemiology , Textile Industry , Adult , Anemia, Hypochromic/diagnosis , Anemia, Hypochromic/drug therapy , Anemia, Hypochromic/etiology , China/epidemiology , Female , Gossypium , Humans , Intrauterine Devices/adverse effects , Iron/therapeutic use , Middle AgedABSTRACT
The incidence of iron deficiency anemia, rickets, and zinc deficiency is very high in Chinese preschool children and a method for prevention is urgently needed. From our studies, it can be seen that a soft drink powder is a convenient vehicle for the supplementation of iron, zinc, calcium, vitamin D, riboflavin, and ascorbic acid. Table salt is also a good, low-cost carrier for iron and zinc, and cow's milk can only be used for the enrichment of vitamins A and D. In our study the therapeutic dose of iron was lower than 3 mg/kg body weight recommended by the WHO Expert Committee. As ascorbic acid can enhance the absorption of iron in the body, so 300 mg vitamin C was added to 100 g of soft drink powder containing 100 mg of elemental iron. Ten g of powder is not only enough for the prevention of iron deficiency anemia but it can also cure iron deficiency anemia within 3 months. One hundred mg of iron in 100 g of table salt is an adequate level, because an adult or a child taking 10 or 5 g of salt will receive 10 and 5 mg of elemental iron respectively. This dosage is adequate for the prevention of anemia. From our results, 10 mg of zinc daily is enough for the prevention and treatment of zinc deficiency in preschool children. Four hundred IU of vitamin D (from fortified soft drink powder or enriched fresh cow's milk) orally-administered daily, is a good way to prevent rickets in infants and young children.