Changes in Thyroid Hormone Are Not Involved in Regulating Brain Protein Synthesis in Adults Rats Fed Ornithine.

Brain protein synthesis and the plasma concentration of growth hormone (GH) are sensitive to dietary ornithine. However, dietary ornithine does not increase brain protein synthesis in hypophysectomized rats. Because hypophysectomy may decrease the secretion of thyroid stimulated hormone (TSH), we assessed whether the regulation of brain protein synthesis was mediated by changes in the plasma concentrations of thyroid hormone and ghrelin in the 6-propyl-2-thiouracil (PTU, thyroid inhibitor)-treated or control adult rats fed ornithine. The four experimental groups consisted of PTU-treated and control (24-wk-old) male rats given 0% or 0.7% ornithine-HCl added to a 20% casein diet. The plasma concentrations of GH and ghrelin, and the fractional rates of protein synthesis and RNA activity [g protein synthesized/(g RNA•d)] in the brains were significantly increased after treatment with the 20% casein + 0.7% ornithine compared with the 20% casein diet alone in both the PTU-treated and control groups. Ornithine supplementation to the basal diet did not affect the plasma concentration of T3. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in the brain regions. The results suggest that dietary ornithine likely increases the rate of brain protein synthesis in control and PTU-treated rats, and that the ornithine-induced increase in the GH concentration may stimulate mainly brain protein synthesis via ghrelin. RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Comparison of the Effects of Ornithine and Arginine on the Brain Protein Synthesis Rate in Young Rats.

Brain protein synthesis and the plasma concentration of growth hormone (GH) are sensitive to dietary ornithine. The purpose of this study was to determine whether dietary arginine, the metabolite of ornithine, affects the brain protein synthesis, and to that end, the effects of arginine on brain protein synthesis were compared with that of ornithine treatment in young rats. Two experiments were done on five or three groups of young rats (5-wk-old) given 0%, 0.25%, 0.5%, 0.7% arginine or 0.7% ornithine-HCl added to a 20% casein diet for 1 d (only one 3 h period) (Experiment 1), or given a diet containing 0% or 0.7% ornithine-HCl or 0.7% arginine added to a 20% casein diet (Experiment 2). The concentrations of plasma growth hormone (GH) and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.7% arginine diet and still more with the 20% casein+0.7% ornithine diet compared with the 20% casein diet alone. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA•d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that the treatment with arginine is likely to increase the concentrations of GH and the rate of brain protein synthesis in rats, and that the effects of arginine on brain protein synthesis and GH concentration were lower than that of ornithine. The RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, p<0.01). These results suggest that the administration of GABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

Influence of GABA on brain protein synthesis mediated by the mammalian target on the rapamycin pathway.

This study determined the influence of γ-aminobutyric acid (GABA) on brain protein synthesis via the mammalian target of rapamycin (mTOR) pathway. Experiments were carried out on three groups of 6-wk-old male rats with 0%, 0.5%, and 1% GABA. The percentage-phosphorylated S6K1 and growth hormone (GH) concentration was significantly increased by the GABA administration. The insulin level was not significantly changed, while the insulin-like growth factor 1 (IGF-1) level was significantly decreased by the GABA administration.

Dietary ornithine affects the tissue protein synthesis rate in young rats.

The purpose of this study was to determine whether ornithine affects the rate of tissue protein synthesis in male rats. Two experiments were done on five or two groups of young rats (5 wk) given diets containing 0.15, 0.3, 0.5 or 0.7% ornithine-HCl added to a 20% casein diet for 1 d (only one 3 h period) (Experiment 1), and given a diet containing 0 or 0.7% ornithine-HCl added to a 20% casein diet for 10 d (Experiment 2). The plasma concentration of growth hormone (GH) was the highest in rats fed 0.5 and 0.7% ornithine added to the 20% casein diet. The fractional rates of protein synthesis in brain regions, liver and gastrocnemius muscle increased significantly with the 20% casein+0.7% ornithine diet compared with the 20% casein diet. In brain regions, liver and gastrocnemius muscle, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. The present results suggest that the treatment of young rats with ornithine is likely to increase the concentration of plasma GH and the rate of protein synthesis in the tissues, and that RNA activity is at least partly related to the fractional rate of tissue protein synthesis.

Effect of dietary ornithine on the brain protein synthesis rate in hypophysectomized aged rats.

The purpose of this study was to determine whether the regulation of brain protein synthesis is mediated through changes in the plasma concentration of growth hormone (GH) when dietary ornithine treatment is manipulated in the hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.7% ornithine-HCl added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.7% ornithine compared with the 20% casein diet alone in the sham-operated rats. However ornithine supplementation to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA•d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that the treatment with ornithine is likely to increase the concentration of GH and the rate of brain protein synthesis in the sham-operated rats only, not in the hypophysectomized rats, and that the ornithine-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Effect of dietary γ-aminobutyric acid on the brain protein synthesis rate in hypophysectomized aged rats.

The purpose of this study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentration of growth hormone (GH) when dietary γ-aminobutyric acid (GABA) treatment was manipulated in hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.5% GABA added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone in the sham-operated rats. However GABA treatment to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that treatment with GABA is likely to increase the concentrations of GH and the rate of brain protein synthesis in sham-operated rats only, not in hypophysectomized rats, and that the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Effect of the quality of dietary amino acids composition on the urea synthesis in rats.

We have shown that urinary urea excretion increased in rats given a lower quality protein. The purpose of present study was to determine whether the composition of dietary amino acids affects urea synthesis. Experiments were done on three groups of rats given diets containing a 10% gluten amino acid mix diet or 10% casein amino acid mix diet or 10% whole egg protein amino acids mix diet for 10 d. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the liver concentration of free serine, glutamic acids and alanine were greater in the group given the amino acid mix diet of lower quality. The fractional and absolute rates of protein synthesis in tissues declined with a decrease in quality of dietary amino acids. The hepatic concentration of ornithine and the activities of hepatic urea-cycle enzymes were not related to the urea excretion. These results suggest that the increased concentrations of amino acids and N-acetylglutamate seen in the liver of rats given the amino acid mix diets of lower quality are likely among the factors stimulating urea synthesis. The protein synthesis in tissues is at least partly related to hepatic concentrations of amino acids. The composition of dietary amino acids is likely to be one of the factors regulating urea synthesis when the quality of dietary protein is manipulated.

Effect of quality and quantity of dietary protein on 4E-BP1 and S6K1 phosphorylation of brains in aged rats.

We have shown that the rate of brain protein synthesis in aged rats depended on the quality and quantity of dietary protein consumed. The purpose of this study was to determine whether the quality and quantity of dietary protein affected the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1) and regulated the brain protein synthesis. Two experiments were done on three groups of 24-wk-old male rats given diets containing 20% casein, 20% gluten, or 20% gelatin (Experiment 1), and 20% casein, 5% casein or 0% casein (Experiment 2) for 10 d. The phosphorylation of S6K1 in both the cerebral cortex and cerebellum, and the phosphorylation of 4E-BP1 in the cerebral cortex declined with a decrease of quality and quantity of dietary protein. The phosphorylation of 4E-BP1 in the cerebellum did not differ among groups. The results suggest that the ingestion of a higher quality and quantity of dietary protein stimulates the phosphorylation of 4E-BP1 and S6K1 in the brain and increases the brain protein synthesis in the aged rats.

Changes in N-acetylglutamate are involved in regulating urea synthesis in rats given a low gluten diet supplemented with L-lysine, L-methinone and L-threonine.

We have shown that urinary urea excretion decreased in rats fed a low gluten diet supplemented with dietary limiting amino acids. The purpose of present study was to determine whether the addition of dietary limiting amino acids to a low gluten diet affected the synthesis and degradation of N-acetylglutamate and regulated urea synthesis. Experiments were done on two groups of rats, given diets containing 10% gluten or 10% gluten+0.5% L-lysine, 0.2% L-threonine and 0.2% L-methionine for 10 d. The urinary excretion of urea, and the liver concentration of N-acetylglutamate, and the liver activity of N-acetylglutamate synthetase decreased with the addition of dietary L-lysine, L-threonine and L-methionine. N-Acetylglutamate concentration in the liver was closely correlated with the N-acetylglutamate synthetase activity in the liver and excretion of urea. The greater degradation of N-acetylglutamate was observed in the group fed the 10% gluten+L-lysine, L-threonine and L-methionine. The hepatic concentration of glutamate and plasma concentration of arginine were not related to the N-acetylglutamate concentration in the liver. These results suggest that the addition of limiting amino acids to the low gluten diet controls the synthesis and degradation of N-acetylglutamate in the liver and lowers urea synthesis.

Dietary gamma-aminobutyric acid affects the brain protein synthesis rate in ovariectomized female rats.

The purpose of this study was to determine whether gamma-aminobutyric acid (GABA) affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to the 20% casein diet. The concentrations of plasma growth hormone (GH) increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the brain regions, GABA treatment to the basal diet elevated significantly the fractional and absolute rates of protein synthesis. In brain regions, the RNA activity [g protein synthesized/(g RNA x d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis. The results suggest that the administration of GABA to ovariectomized female rats is likely to increase the concentrations of plasma GH and the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Role of estrogen receptors and aromatase on brain protein synthesis rates in ovariectomized female rats fed genistein.

We have reported that the dietary addition of genistein, a phytoestrogen found abundantly in soy products, stimulates brain protein synthesis rates of ovariectomized female rats. In the present study, we determine whether stimulation of brain protein synthesis rates in ovariectomized female rats by the dietary addition of genistein was conducted via estrogen receptors and aromatase-mediating actions. After ovariectomy, Wistar female rats were treated with genistein, the estrogen receptor antagonist ICI 182,780, and/or fadrozole a systemic aromatase inhibitor. In the cerebral cortex, the cerebellum and the hypothalamus, the fractional (Ks) rates of protein synthesis were increased by the dietary addition of genistein. These effects of genistein were inhibited by the administration of ICI 182,780 and fadrozole. However, the degrees to which ICI 182,780 and fadrozole inhibited the effects of genistein differed depending on the brain region. This result suggests that dietary genistein elevates the rate of protein synthesis in the brain of ovariectomized female rats. In addition, the estrogen receptors of the brain and the aromatase of the peripheral tissue and brain are, at least partly, related to the rate of brain protein synthesis caused by genistein.

The growth hormone affects the brain protein synthesis rate in hypophysectomized aged rats.

The purpose of this study was to determine whether the growth hormone (GH) affects the rate of brain protein synthesis in hypophysectomized aged rats. Experiments were conducted on three groups of 24-wk-old male rats: group 1 were hypophysectomized to reduce the level of plasma GH, group 2 were hypophysectomized and treated with GH and group 3 were sham-operated controls. The fractional rates of protein synthesis in the brains of hypophysectomized rats with GH were significantly greater than those in hypophysectomized rats without GH. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA.d)] significantly correlated with the fractional rate of protein synthesis (r>0.88, p<0.001). The RNA concentration (mg RNA/ g protein) was also related to the fractional rate of protein synthesis in these organs (r>0.56, p<0.05). The results suggest that the treatment of GH to hypophysectomized aged rats is likely to increase the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Role of N-acetylglutamate turnover in urea synthesis of rats given proteins of different quality.

The purpose of this study was to find whether the synthesis and degradation of N-acetylglutamate would affect urea synthesis when the dietary protein quality was manipulated. Experiments were done on three groups of rats given diets containing 10 g gluten, 10 g casein or 10 g whole egg protein/100 g for 10 d. The urinary excretion of urea, the liver concentrations of N-acetylglutamate and free glutamate, the liver activity of N-acetylglutamate synthetase increased with the decline in quality of dietary protein. A reverse correlation was observed between the liver N-acetylglutamate degradation and liver Nacetylglutamate concentration. N-Acetylglutamate concentration in the liver was closely correlated with the concentration of glutamate and the N-acetylglutamate synthetase activity in the liver, and excretion of urea. These results suggest that the greater synthesis and the lower degradation rate of N-acetylglutamate in the liver of rats given the lower quality of protein increase the liver concentration of N-acetylglutamate and stimulate urea synthesis.

Effect of adding dietary methionine to a low soy protein diet on the brain protein synthesis rate in ovariectomized female rats.

A deficiency of sex hormones affects brain function in mammals, including the decrease of protein synthesis. Recently, we have shown that the protein synthesis in the brain depended on the quality of dietary protein in ovariectomized female rats. The methionine is the first limiting amino acid for the recommended dietary allowance of amino acids in soy protein. The purpose of this study was to determine whether the addition of dietary methionine affected the rate of brain protein synthesis in ovariectomized female rats fed on the soy protein diet. Experiments were conducted on two groups of ovariectomized female rats (24 week) given the diets containing 5% soy protein or 5% soy protein + 0.2% methionine for 10 d. The fractional rates of protein synthesis in cerebral cortex and cerebellum significantly increased with an addition of dietary methionine. In the brain, the RNA activity [g protein synthesized/((g RNA) x d)] was significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg of RNA/g of protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that the addition of limiting amino acid for the low soy protein elevates the rate of protein synthesis in the brain of ovariectomized female rats, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Changes in tissue protein synthesis are involved in regulating urea synthesis in rats given proteins of different quality.

The purpose of present study was to determine whether the regulation of urea synthesis is mediated through changes in supply of amino acids by protein synthesis and whether the concentration of ammonia, or activities of amino acid catabolizing enzymes, regulate urea synthesis when the dietary protein quality is manipulated. Experiments were done on three groups of rats given diets containing 10 g gluten, 10 g casein or 10 g whole egg protein/100 g for 10 d. The urinary excretion of urea, and the liver concentrations of glutamate, serine and alanine increased with a decrease in quality of dietary protein. The fractional and absolute rates of protein synthesis in tissues declined with the decrease in quality of dietary protein quality. The ammonia concentration in plasma and liver, and activities of hepatic amino acid catabolizing enzymes was not related to urea excretion under these conditions. These results suggest that the lower protein synthesis seen in tissues of rats given the lower quality of protein is likely to be one of the factors to increasing the supply of amino acids and stimulating urea synthesis.

Role of N-acetylglutamate concentration and ornithine transport into mitochondria in urea synthesis of rats given proteins of different quality.

The purpose of this study was to find whether the concentration of N-acetylglutamate and ornithine transport into mitochondria would regulate urea synthesis when the dietary protein quality was manipulated. Experiments were done on three groups of rats given diets containing 10 g of gluten, 10 g of casein, or 10 g of whole egg protein/100 g for 10 days. The plasma concentration and urinary excretion of urea, the liver concentration and synthesis of N-acetylglutamate, the liver concentrations of glutamate and lysine, and the liver ornithine transport into mitochondria increased with the decrease in quality of dietary protein. A reverse correlation was observed between the activities of urea cycle enzymes, the plasma concentration of arginine, and urinary excretion of urea under these conditions. N-Acetylglutamate concentration and ornithine transport into mitochondria in the liver were closely correlated with the excretion of urea. These results suggest that greater N-acetylglutamate concentration and ornithine transport into isolated mitochondria in the liver of rats, given the lower quality of protein, stimulate urea synthesis and that the concentrations of glutamate and lysine in the liver are at least partly related to the hepatic N-acetylglutamate synthesis and ornithine transport, respectively.

Dietary genistein affects brain protein synthesis rates in ovariectomized female rats.

The purpose of this study was to determine whether genistein affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were conducted on three groups of 12-wk-old female rats: those in group 1 were ovariectomized to reduce the level of plasma sex hormone; those in group 2 were ovariectomized and fed diets containing 0.01% genistein; and those in group 3 were sham-operated controls. The fractional rates of protein synthesis in the brain of ovariectomized rats fed genistein were significantly greater than those in ovariectomized rats without genistein treatment. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA.d)] significantly correlated (r > 0.86, P < 0.001) with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that the addition of genistein to the diet of ovariectomized female rats is likely to increase the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Effects of quantity and quality of dietary protein on the brain polysome profile in aged rats.

The purpose of this study was to determine whether the quantity and quality of dietary protein affected the polysome profile of the brain in aged rats. Two experiments were done on three groups of aged rats (30 wk) given the diets containing 20% casein, 5% casein, or 0% casein (experiment 1), and 20% casein, 20% gluten, or 20% gelatin (experiment 2) for 10 d. The aggregation in brain ribosomes declined with a decrease of quantity and quality of dietary protein except in the hippocampus. The RNA concentration (mg RNA/g protein) did not differ among the three groups varying the dietary protein in any brain regions. The results suggest that the higher quantity and quality of dietary protein improves the polysome profile in the brain of aged rats, and that the polysome profile is at least partly related to the mechanism by which the dietary protein affects brain protein synthesis in aged rats.

Effect of dietary protein quantity and quality on the brain protein synthesis rate in ovariectomized female rats.

The purpose of this study was to determine whether the quantity and quality of dietary protein affected the rate of brain protein synthesis in ovariectomized female rats. Two experiments were conducted on the ovariectomized female rats (12 weeks old) given diets containing 20%, 5%, or 0% casein (experiment 1) and 20% casein, 20% soy protein, 20% gluten, or 20% gelatin (experiment 2) for 10 d, respectively. The fractional rates of protein synthesis in the brain declined with a decrease of the quantity and quality of dietary protein. In the brain, the RNA activity [g of protein synthesized/((g of RNA) d)] was significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg of RNA/g of protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that the rate of protein synthesis in the brain declines with the decrease of the quantity and quality of dietary protein in ovariectomized female rats, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.