Protein Synthesis In Liver Research Articles

Evidence for an alteration of plasma and liver proteins response to dexamethasone in aging rats

The aim of this study was carried out to analyse the liver and plasma proteins response to dexamethasone in adult (6–8 months) and old (24 months) rats in order to ascertain the involvement of glucocorticoids in the aging process. The animals received dexamethasone (Dex) for 5 or 6 days. As Dex decreased food intake, all groups were pair fed to dexamethasone-treated old rats. The synthesis of mixed plasma and liver proteins (assessed by a flooding dose of [ 13C] valine) was similarly greatly improved in adult and old rats after Dex treatment. However, the level of mixed plasma proteins was only slightly increased. When specific plasma proteins were assessed, a similar increase in the concentration of albumin and alpha1 acid glycoprotein was observed in adult and old rats. By contrast, fibrinogen decreased to a greater extend in old rats and alpha2 macroglobulin became undetectable in old animals. It was concluded that the response of plasma and liver proteins to Dex was altered in old rats and may contribute to the pathogenesis of several diseases which occur during aging.

Age-related changes of protein- and RNA-synthetic processes in experimental hyper- and hypothyroidism.

The rate of liver and plasma protein synthesis and the activity of liver RNA polymerases 1 and 2 were investigated in rats of various age under experimental hyper- and hypothyroidism. The rate of plasma protein synthesis decreased with age more dramatically than that of liver proteins. Hyper- and hypothyroidism exerted opposite effects on protein synthesis in rats: stimulation and inhibition, respectively. The manifestation of these effects was age related. The thyroid status of animals also influenced the balance of protein synthesis. Thyroxin administration caused preferential incorporation of a label into blood plasma proteins. Changes of thyroid status of old animals insignificantly affected the absolute values of the label incorporation into proteins and the ratio of the label incorporation into local and secreted liver proteins. Age-related decrease of total hepatic nuclear RNA-polymerase activity was due to reduction of the template-bound functionally active forms of RNA-polymerases 1 and 2. Administration of thyroxin caused initial redistribution of the enzyme activity between template-bound and free fractions accompanied by the increase of template bound RNA-polymerases. Prolonged hormonal stimulus also caused an increase of free RNA-polymerases, which reflects the increased synthesis of these enzymes. Mecrazolyl administration reduced the activity of RNA-polymerase 1 and 2. All age groups were characterized by preferential reduction of the bound form. RNA-polymerase 2 activity decreased to a greater extent than that of RNA-polymerase 1. The data suggest age-determined reactions of the body to altered thyroid status.

Ouabain‐sensitive respiration and protein synthesis in duodenal mucosa and liver in rats fed increasing levels of pea fibre or protein and housed in 18 or 28°C environments

SummarySeventy‐two Wistar rats were used in two studies to investigate the effect of environmental temperature (18 or 28°C), and increasing levels of dietary fibre (low, 68 g/kg dry matter (DM); medium 110 g/kg DM; high, 157 g/kg DM) and protein (low, 91 g/kg DM; medium, 171 g/kg DM; high, 262 g/kg DM) on respiration attributable to Na+,K+‐ATPase activity and protein synthesis in duodenal mucosa and liver of rats. In vitro O2 consumption in tissues was measured polarographically using a Clark‐style YSI biological O2 monitor. Whole‐body O2 consumption was measured with two open‐circuit respiration chambers. Whole‐body O2 consumption was higher (p < 0.05) at 18°C than at 28°C. Rats fed the low protein diet had significantly higher (p < 0.05) whole‐body O2 consumption than those fed the medium or high protein diet. Compared with 28°C, the environmental temperature of 18°C caused an increase (p < 0.05) in total O2 consumption and O2 consumption attributable to Na+,K+‐ATPase activity in duodenal mucosa. There was no effect (p > 0.05) of environmental temperature on total O2 consumption, Na+,K+‐ATPase activity attributable to protein synthesis dependent on O2 consumption in the liver. Total O2 consumption and O2 consumption attributable to Na+,K+‐ATPase activity increased (p < 0.05) in duodenal mucosa in rats fed the low level of dietary fibre compared with rats fed the medium level of dietary fibre. In vitro O2 consumption determined in duodenal mucosa and in liver did not always correspond to whole‐body O2 consumption. This may indicate that respiration in the duodenum and liver adapts differently and may not reflect changes in whole‐body respiration in response to dietary modification and changes in thermal environment.

The effects of T-2 toxin exposure on liver drug metabolizing enzymes in rabbit

High doses of T-2 toxin are known to decrease protein synthesis and mono-oxygenase activities in rat liver. The purpose of this study was to investigate whether exposure at a low dose could alter the normal metabolism of the xenobiotic by the liver. Three doses of T-2 toxin, dissolved in olive oil, were orally and daily administered to New Zealand white rabbits for five days. At 0.5mg/kg, three of the five animals died, whereas only a weak decrease in body weight gain and moderate signs of toxicity occurred in rabbits receiving 0.25mg/kg/day, and the body weight increased without signs of toxicity at 0.1mg/kg/day. At 0.25mg/kg/day, total liver microsomal P450 content, and the activities of aminopyrine and benzphetamine N-demethylases, pentoxyresorufin O-depentylase, glutathione S-transferases accepting 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates, were decreased. By contrast, ethylmorphine and erythromycin N-demethylases, ethoxyresorufin and methoxyresorufin O-dealkylases, aniline hydroxylase, and UDP-glucuronyltransferase accepting p-nitrophenol as substrate, were unaffected. The expression of P450 1A1, 1A2, 2A1, and 2B4, but not P450 2C3 and 3A6, were also decreased, whereas microsomal conjugated dienes, fluorescent substances, and malondialdehyde contents were increased. At 0.1mg/kg/day, neither significant effects on drug metabolizing enzymes nor microsomal oxidative damages were obtained. Taken together, these results suggest that a short exposure time to the mycotoxin would not be associated with significant changes in the normal metabolism of xenobiotics by the liver.

Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process.

Protein synthesis is repressed in both skeletal muscle and liver after a short-term fast and is rapidly stimulated in response to feeding. Previous studies in rats and pigs have shown that the feeding-induced stimulation of protein synthesis is associated with activation of the 70-kDa ribosomal protein S6 kinase (S6K1) as well as enhanced binding of eukaryotic initiation factor eIF4E to eIF4G to form the active eIF4F complex. In cells in culture, hormones and nutrients regulate both of these events through a protein kinase termed the mammalian target of rapamycin (mTOR). In the present study, the involvement of mTOR in the feeding-induced stimulation of protein synthesis in skeletal muscle and liver was examined. Pigs at 7 days of age were fasted for 18 h, and then one-half of the animals were fed. In addition, one-half of the animals in each group were administered rapamycin (0.75 mg/kg) 2 h before feeding. The results reveal that treating 18-h fasted pigs with rapamycin, a specific inhibitor of mTOR, before feeding prevented the activation of S6K1 and the changes in eIF4F complex formation observed in skeletal muscle and liver after feeding. Rapamycin also ablated the feeding-induced stimulation of protein synthesis in liver. In contrast, in skeletal muscle, rapamycin attenuated, but did not prevent, the stimulation of protein synthesis in response to feeding. The results suggest that feeding stimulates hepatic protein synthesis through an mTOR-dependent process involving enhanced eIF4F complex formation and activation of S6K1. However, in skeletal muscle, these two processes may account for only part of the stimulation of protein synthesis, and thus additional steps may be involved in the response.

Effects of tumor necrosis factor-binding protein on hepatic protein synthesis during chronic sepsis.

Cytokines are thought to play a role in the stimulation of protein synthesis in liver during inflammation and sepsis. We previously showed that administration of tumor necrosis factor-binding protein (TNFbp) prevents the sepsis-induced inhibition of protein synthesis in skeletal muscle. The purpose of the present set of experiments was to investigate the effect of TNFbp on hepatic protein synthesis and its ability to modulate the mechanisms responsible for increased hepatic protein synthesis during chronic (5-day) intraabdominal sepsis. We examined the effects of TNFbp on hepatic protein synthesis during sepsis in four groups of rats: control, control + TNFbp, septic, and septic + TNFbp. Saline (1.0 ml) or TNFbp (1 mg/kg, 1.0 ml) was injected daily starting 4 h prior to the induction of sepsis. The effect of sepsis and TNFbp administration on hepatic protein synthesis in vivo was examined 5 days later. Sepsis increased the rate of protein synthesis by 35% relative to controls. Accelerated rates of protein synthesis were accompanied by increased total RNA content, eukaryotic initiation factor (eIF) 2alpha content, and phosphorylation of p70S6 kinase. Injection of TNFbp into septic rats for 5 days did not diminish the sepsis-induced stimulation of hepatic protein synthesis. Compared with controls, septic rats treated with TNFbp also showed elevated total RNA content, elF2alpha content, and phosphorylation of p70S6 kinase. No significant differences in any of the parameters measured were observed between untreated and TNFbp-treated septic rats. Treatment of control animals with TNFbp for 5 days was without effect on any of the parameters examined. TNFbp did not prevent the sepsis-induced stimulation of hepatic protein metabolism or modulate the septic-induced changes in factors regulating protein synthesis. Global rates of protein synthesis in livers from septic rats are accelerated by increases in the abundance or activity of components of translational apparatus.

Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis.

Plasma albumin is well known to decrease in response to inflammation. The rate of albumin synthesis from both liver and plasma was measured in vivo by use of a large dose of L-[(2)H(3)-(14)C]valine in rats injected intravenously with live Escherichia coli and in pair-fed control rats during the acute-phase period (2 days postinfection). The plasma albumin concentration was reduced by 50% in infected rats compared with pair-fed animals. Infection induced a fall in both liver albumin mRNA levels and albumin synthesis relative to total liver protein synthesis. However, absolute liver albumin synthesis rate (ASR) was not affected by infection. In plasma, albumin fractional synthesis rate was increased by 50% in infected animals compared with pair-fed animals. The albumin ASR estimated in the plasma was similar in the two groups. These results suggest that hypoalbuminemia is not due to reduced albumin synthesis during sepsis. Moreover, liver and plasma albumin ASR were similar. Therefore, albumin synthesis measured in the plasma is a good indicator of liver albumin synthesis.

Provision of rhIGF-I/IGFBP-3 complex attenuated development of cancer cachexia in an experimental tumor model

Tumor growth is associated with development of cachexia which includes progressive wasting and anorexia. Our previous studies have indicated that insulin like growth factor-I (rhIGF-I) in complex with its binding protein 3 (IGFBP 3), but not free IGF-I, was a potent stimulator of muscle protein synthesis in rats with chronic undernutrition. The aim of the present study was to evaluate the effect of rhIGF-I/IGFBP-3 on the development of cancer cachexia, and to assess safety data on net tumor growth and progression during treatment.Methods: A methylcholantrene induced sarcoma was implanted s.c. in C 57 bl mice. The animals were provided with rhIGF-I/rhIGFBP-3 (5 μg/g bw) i.v. twice daily (n= 18). Controls were provided with saline (n= 20). Body weight and food intake were registered daily. Net tumor growth was measured over 10 days. Protein synthesis in liver and muscle, as well as plasma concentrations of glucose, insulin, IGF-I and amino acids were measured at the end of the study.Results: tumor size did not differ between control mice and rhIGF-I/rhIGFBP-3 treated mice (1.5 ± 0.1 g wet tumor weight vs 1.6 ± 0.2 g respectively). Saline treated tumor bearing controls lost 9.1 ± 1.3 % body weight over 10 days due to rapid tumor growth while rhIGF-I/rhIGFBP-3 provision attenuated weight loss to 5.6 ± 1.3% of body weight in study mice (P< 0.05). Food intake was improved and blood glucose concentration was reduced from 7.1 ± 0.5 to 5.8 ± 0.2 (P< 0.05) in response to treatment.Conclusion: Our results demonstrate that rhIGF-I/rhIGFBP-3 complex did not affect net tumor growth. Moreover rhIGF-I/rhIGFBP-3 complex improved tumor-host nutritional state by improving food intake, attenuating weight loss and improving glucose metabolism.

Impaired Protein Synthesis Induced by Acute Alcohol Intoxication Is Associated With Changes in eIF4E in Muscle and eIF2B in Liver

Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure. Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and tissues were examined 2.5 hr later. Rates of protein synthesis in vivo were determined by [3H]phenylalanine incorporation into protein, and various eukaryotic initiation factors (eIFs) were quantitated by Western blot analysis to identify possible mechanisms for regulating translation. Protein synthesis in gastrocnemius and liver was decreased (39% and 21%, respectively) after alcohol administration, compared with saline-injected control animals. Alcohol administration did not alter tissue RNA content but diminished translational efficiency in muscle (43%) and liver (24%). Hepatic eIF2B activity was decreased 24% in alcohol-treated rats, and this was associated with a 95% increase in eIF2alpha phosphorylation. However, alcohol did not alter the amount of 4E-binding protein 1 (4E-BP1) bound to eIF4E, cIF4E bound to eIF4G, or the phosphorylation state of either 4E-BP1 or eIF4E. In contrast to liver, neither eIF2B activity nor the phosphorylation of eIF2alpha was affected in muscle of alcohol-treated rats. However, acute alcohol intoxication increased binding of 4E-BP1 to eIF4E (113%), decreased the amount of cIF4E bound to cIF4G (81%), and decreased the amount of 4E-BP1 in the phosphorylated gamma-form (77%). The plasma concentrations of insulin and insulin-like growth factor-I were unchanged by alcohol, but muscle insulin-like growth factor-I messenger ribonucleic acid abundance was decreased 35%. These data suggest that acute alcohol intoxication decreases translation initiation and protein synthesis in liver and muscle via different mechanisms. Changes in eIF2B appear to predominate in liver, whereas alterations in eIF4E availability appear more critical in skeletal muscle for controlling translation initiation.

Therapeutic effect of melatonin on carbon tetrachloride-induced acute liver injury in rats.

The therapeutic effect of melatonin on acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). Melatonin (10, 50, or 100 mg/kg body weight [BW]) was intraperitoneally administered to male Wistar rats 6 hr after intraperitoneal injection of CCl4 (1.6 g/kg BW) at which time an apparent liver injury occurred. This post-melatonin administration dose dependently prevented the progression of liver injury at 24 hr after CCl4 injection, judging from the levels of serum transaminases, indices of liver cell damage. Rats injected with CCl4 alone showed an increase in liver lipid peroxide (LPO) content and a decrease in liver reduced glutathione content at 6 and 24 hr after the injection. The post-melatonin administration dose dependently ameliorated both changes found at 24 hr after CCl4 injection. Rats injected with CCl4 alone showed an increase in liver triglyceride (TG) content and decreases in serum TG concentration and liver tryptophan 2,3-dioxygenase (TDO) activity, a marker of the inhibition of liver protein synthesis by CCl4, at 6 and 24 hr after the injection, and also a decrease in serum albumin concentration at 24 hr. The changes in serum TG, albumin concentration, liver TG content, and TDO activity found at 24 hr after CCl4 injection were not ameliorated by the post-administration of melatonin. The same administration of melatonin dose dependently reduced liver LPO content in CCl4-untreated rats. These results indicate that melatonin exerts a therapeutic effect on CCl4-induced acute liver injury in rats, possibly through its antioxidant action.

Various Macronutrient Intakes Additively Stimulate Protein Synthesis in Liver and Muscle of Food-Deprived Chicks

We investigated the influence of refeeding food-deprived chicks with either protein, carbohydrate, fat or combinations thereof on the rates of liver and muscle protein synthesis. After 2 d of food-deprivation, chicks were given individual or mixed protein, carbohydrate and fat. At 30 min after refeeding, the protein fractional synthesis rate (K(s)) was measured by a large dose injection of L-[2,6-(3)H]phenylalanine. When chicks were food-deprived for 2 d, liver K(s) was 67% lower and muscle fractional synthesis rate was half that of well-fed controls. Upon refeeding starved chicks a complete diet, K(s) in the liver and muscle returned to the level of fed controls within 30 min. When food-deprived chicks were refed protein alone or two of the three macronutrients, liver and muscle K(s) were significantly higher than those in the starved group. There was no effect of refeeding with carbohydrate or fat alone. Plasma glucose concentration was significantly greater than in fed or starved groups in chicks refed the complete diet, carbohydrate or carbohydrate mixed with either protein or fat. Refeeding chicks with the various macronutrients did not affect the plasma insulin or insulin-like growth factor-I concentrations. These results suggest that intakes of individual macronutrients additively increase liver and muscle protein synthesis and that the acute increase in muscle protein synthesis after refeeding chicks diets containing the three macronutrients was mainly regulated by the change in ribosomal efficiency.

Effects of Adding Dietary Lysine to a Low Gluten Diet on the Brain Protein Synthesis Rate in Aged Rats

The purpose of this study was to find whether the addition of dietary lysine affected the rate of brain protein synthesis in aged rats fed on a gluten diet. Experiments were done on two groups of aged rats (30 wk) given the diets containing 5% gluten or 5% gluten + 0.3% lysine for 10 d. The fractional rates of protein synthesis in brain, liver, and kidney increased with an addition of dietary lysine. In brain, liver, and kidney, the RNA activity [g protein synthesized/(g RNA x d)] was 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 results suggest that the addition of the limiting amino acid for the low quality protein elevates the rate of protein synthesis in the brain of aged rats, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Leucine, Glutamine, and Tyrosine Reciprocally Modulate the Translation Initiation Factors eIF4F and eIF2B in Perfused Rat Liver

Leucine, glutamine, and tyrosine, three amino acids playing key modulatory roles in hepatic proteolysis, were evaluated for activation of signaling pathways involved in regulation of liver protein synthesis. Furthermore, because leucine signals to effectors that lie distal to the mammalian target of rapamycin, these downstream factors were selected for study as candidate mediators of amino acid signaling. Using the perfused rat liver as a model system, we observed a 25% stimulation of protein synthesis in response to balanced hyperaminoacidemia, whereas amino acid imbalance due to elevated concentrations of leucine, glutamine, and tyrosine resulted in a protein synthetic depression of roughly 50% compared with normoaminoacidemic controls. The reduction in protein synthesis accompanying amino acid imbalance became manifest at high physiologic concentrations and was dictated by the guanine nucleotide exchange activity of translation initiation factor eIF2B. Paradoxically, this phenomenon occurred concomitantly with assembly of the mRNA cap recognition complex, eIF4F as well as activation of the 70-kDa ribosomal S6 kinase, p70(S6k). Dual and reciprocal modulation of eIF4F and eIF2B was leucine-specific because isoleucine, a structural analog, was ineffective in these regards. Thus, we conclude that amino acid imbalance, heralded by leucine, initiates a liver-specific translational fail-safe mechanism that deters protein synthesis under unfavorable circumstances despite promotion of the eIF4F complex.

Change in protein synthesis in rats fed a high phosphorus diet

The concentration of albumin in serum, the level of expression of albumin mRNA, polysome profiles and peptide synthesis activity in the liver were investigated in order to assess the level of protein synthesis in rats fed either a high phosphorus diet containing 1.5% phosphorus or a control diet containing 0.5% phosphorus for 3 weeks. In the rats fed the high phosphorus diet, body weight gain, food efficiency and serum albumin concentration decreased, and the albumin/globulin ratio also decreased compared with the control group. A low level of albumin mRNA expression was observed, consistent with the decrease in serum albumin concentration. The peptide synthesis activity in liver as determined in vitro was lower in the group fed the high phosphorus diet than in the control group. The abundance of heavier polysomes considered to influence protein synthesis in vivo was decreased in the rats given the high phosphorus diet compared with the control group. The results suggest that high phosphorus intake caused a decrease in protein synthesis in liver.

Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E.

The present study examined potential cellular mechanisms responsible for the inhibition of protein synthesis in liver after chronic alcohol consumption. Rats were maintained on an alcohol-containing diet for 14 wk; control animals were fed isocalorically. Hepatic ATP content was not different in alcohol-fed and control animals. No alcohol-induced reduction in total hepatic RNA content (an estimate of ribosomal RNA) was detected, suggesting that alcohol decreased translational efficiency. Alcohol feeding increased the proportion of 40S and 60S ribosomal subunits in the nonpolysome-associated fraction by 30%. To identify mechanisms responsible for the impairment in initiation, several eukaryotic initiation factors (eIF) were analyzed. Alcohol feeding decreased hepatic eIF2B activity by 36%. This reduction was associated with a 20% decrease in eIF2Bepsilon content and a 90% increase in eIF2alpha phosphorylation. Alcohol also dramatically influenced the distribution of eIF4E. Compared with pair-fed control values, alcohol feeding increased the amount of eIF4E present in the inactive 4E-binding protein 1 (4E-BP1). eIF4E complex by 80% and decreased binding of eIF4G to eIF4E by 70%. However, the phosphorylation status of 4E-BP1 and eIF4E was not altered by alcohol. Although the plasma concentrations of threonine, proline, and citrulline were mildly decreased, the circulating amount of total amino acids was not altered by alcohol feeding. In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability.

Lower recovery of muscle protein lost during starvation in old rats despite a stimulation of protein synthesis.

Sarcopenia could result from the inability of an older individual to recover muscle lost during catabolic periods. To test this hypothesis, we compared the capacity of 5-day-refed 12- and 24-mo-old rats to recover muscle mass lost after 10 days without food. We measured gastrocnemius and liver protein synthesis with the flooding-dose method and also measured nitrogen balance, 3-methylhistidine excretion, and the gene expression of components of proteolytic pathways in muscle comparing fed, starved, and refed rats at each age. We show that 24-mo-old rats had an altered capacity to recover muscle proteins. Muscle protein synthesis, inhibited during starvation, returned to control values during refeeding in both age groups. The lower recovery in 24-mo-old rats was related to a lack of inhibition of muscle proteolysis during refeeding. The level of gene expression of components of the proteolytic pathways did not account for the variations in muscle proteolysis at both ages. In conclusion, this study highlights the role of muscle proteolysis in the lower recovery of muscle protein mass lost during catabolic periods.

Effects of Deletion-Type Human Hepatocyte Growth Factor on Murine Septic Model

Background. Sepsis is known to be the main cause of multiple organ failure. The liver especially is vulnerable to the stress of infection. In this study, the effects of deletion-type human hepatocyte growth factor (dHGF) on a murine septic model were studied.Materials and methods. Sepsis was induced in male adult Sprague–Dawley rats by cecal ligation and puncture method (CLP). Controls were given a sham operation. Intravenous injection of 1000 μg/kg dHGF or the same volume of vehicle was given every 12 h for 3 days before and/or after the CLP from a central vein catheter inserted 1 week prior to the operation. The daily percentage of survival after CLP was followed up for 1 week, and blood samples and liver specimens were collected from the surviving animals 72 h after CLP or sham operation.Results. The survival rate, the degree of liver damage and liver protein synthesis, and coagulation function were all favorable in the dHGF-treated animals compared to the untreated animals. Immunohistochemical staining showed that dHGF prevented the disappearance of thrombomodulin (TM) in liver sinusoid endothelium.Conclusions. dHGF appears to prevent liver injury caused by disturbance of microcirculation through preservation of TM expression and the antithrombotic function in the endothelium of sinusoids. dHGF also facilitates repair of damaged hepatic tissue by stimulating regeneration of the cells and by preserving hepatic functions such as protein synthesis. dHGF exerts protective effects on even quiescent hepatocytes, but is most effective on injured but competent hepatocytes.

Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats.

The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT). Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) ROLT, 500 microg/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated. dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that underwent syngeneic ROLT. In the rats that underwent allogeneic ROLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT. Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection.

Alleviation of carbon tetrachloride-induced chronic liver injury and related dysfunction by L-tryptophan in rats.

We examined whether L-tryptophan (Trp) alleviates carbon tetrachloride (CCl4)-induced chronic liver injury and related dysfunction. Fifty rats were classified into four groups: the first (15 rats) served as the control; the second (10 rats) received subcutaneous injections of CCl4 (1.0 mL/kg) twice weekly for 8 weeks; the third (15 rats) received daily intraperitoneal injections of Trp (50 mg/kg) for 2 weeks after 6 weeks of CCl4 treatment; the fourth (10 rats) received both treatments. The activities of serum transaminases and the content of liver total hydroxyproline increased after 6 and 8 weeks of CCl4 treatment. The concentrations of serum albumin and liver protein and the in vitro activity of liver protein synthesis fell after 8 weeks of the treatment. Trp administration alleviated all these changes. At 6 and 8 weeks of CCl4 treatment the serum triglyceride concentration fell, whereas the liver triglyceride and lipid peroxide concentrations were elevated. Trp administration hardly affected these changes. These results indicate that Trp alleviates CCl4-induced chronic liver injury possibly by maintaining the activity of protein synthesis.

The effects of elevated summer temperature and sublethal pollutants (ammonia, low pH) on protein turnover in the gill and liver of rainbow trout ( Oncorhynchus mykiss) on a limited food ration

Protein synthesis, degradation and growth of the liver and gills were determined in juvenile rainbow trout ( Oncorhynchus mykiss) fed a limited ration and exposed for 90 days to normal or elevated summer temperatures (+2°C above ambient) and either low pH (5.2) in softwater or 70 μM total ammonia in hardwater. The limited ration resulted in low rates of growth (<0.80% per day) and protein synthesis in all fish. In softwater, whole-body growth was significantly inhibited by elevated temperature but stimulated by low pH, although tissue protein metabolism was generally unaffected by these treatments. There was no significant difference in final size between the groups of fish in hardwater, but liver protein synthesis and degradation were significantly lower at +2°C, the reduction in synthesis being due to an inhibition of both the capacity for protein synthesis, C s and the RNA translational efficiency, k RNA. Gill protein metabolism was unaffected by the experimental treatments in trout in hardwater. The authors conclude that a global warming scenario would be detrimental to protein synthesis and growth in freshwater fish under conditions of food limitation in summer, and when late summer temperatures approached the upper thermal limit of the species, regardless of food availability.