Aflatoxin B1 induced inhibition of liver protein synthesis in vivo and its role in fatty liver

1971 ◽  
Vol 20 (10) ◽  
pp. 2825-2831 ◽  
Author(s):  
K. Suryanarayana Rao
1970 ◽  
Vol 16 (10) ◽  
pp. 959-963 ◽  
Author(s):  
R. W. Detroy ◽  
C. W. Hesseltine

The effect of two inhibitors on the formation of aflatoxin B1 synthetase activity in strain NRRL 2999 Aspergillus parasiticus has been studied. Aflatoxin B1 synthesizing activity was measured in vivo by incorporation of the 14C-methionine methyl group into aflatoxin B1. Cycloheximide at a concentration of 150 μg/ml blocks protein synthesis completely. If addition of cycloheximide is made before B1 synthetase appears, no activity accumulates; if added during accumulation, activity is frozen at the level reached at the time of addition. The cycloheximide effect is reversible since morphogenesis, total protein synthesis, and aflatoxin B1 synthetase activity all resume after removal of the inhibitor.DL-p-Fluorophenylalanine partially inhibits aflatoxin B1 synthesis in vivo; however, its effect upon macromolecular synthesis is incomplete even at high concentration levels. Once formed, the aflatoxin synthetase appears to maintain B1 synthesis when further protein synthesis is blocked; i.e., it is not rapidly degraded.


1992 ◽  
Vol 262 (2) ◽  
pp. C445-C452 ◽  
Author(s):  
T. C. Vary ◽  
S. R. Kimball

The regulation of protein synthesis was determined in livers from control, sterile inflammatory, and septic animals. Total liver protein was increased in both sterile inflammation and sepsis. The rate of protein synthesis in vivo was measured by the incorporation of [3H]phenylalanine into liver proteins in a chronic (5 day) intra-abdominal abscess model. Both sterile inflammation and sepsis increased total hepatic protein synthesis approximately twofold. Perfused liver studies demonstrated that the increased protein synthesis rate in vivo resulted from a stimulation in the synthesis of both secreted and nonsecreted proteins. The total hepatic RNA content was increased 40% only in sterile inflammation, whereas the translational efficiency was increased twofold only in sepsis. The increase in translational efficiency was accompanied by decreases in the amount of free 40S and 60S ribosomal subunits in sepsis. Rates of peptide-chain elongation in vivo were increased 40% in both sterile inflammation and sepsis. These results demonstrate that sepsis induces changes in the regulation of hepatic protein synthesis that are independent of the general inflammatory response. In sterile inflammation, the increase in protein synthesis occurs by a combination of increased capacity and translational efficiency, while in sepsis, the mechanism responsible for accelerated protein synthesis is an increased translational efficiency.


1968 ◽  
Vol 109 (1) ◽  
pp. 87-91 ◽  
Author(s):  
S. Villa-Treviño ◽  
D. D. Leaver

1. Aflatoxin and the pyrrolizidine alkaloid retrorsine inhibited the incorporation of labelled amino acids into rat liver and plasma proteins in vivo. Inhibition was greater and detected earlier with retrorsine (1hr.) than with aflatoxin (3hr.). 2. Both toxins affected the liver ribosomal aggregates, causing increases in the proportion of monomers plus dimers. The effect of retrorsine was greater than that of aflatoxin. 3. Incorporation of labelled amino acids into proteins of cell-free preparations of liver from rats treated with aflatoxin was lower than in control preparations. The main site of inhibition appeared to be the ribosomes. 4. Both toxins inhibited the incorporation of orotate into liver nuclear RNA 1hr. after administration.


1987 ◽  
Vol 241 (2) ◽  
pp. 491-498 ◽  
Author(s):  
D Pérez-Sala ◽  
R Parrilla ◽  
M S Ayuso

We investigated the effects of administration of single amino acids to starved rats on the regulation of protein synthesis in the liver. Of all the amino acids tested, only alanine, ornithine and proline promoted statistically significant increases in the extent of hepatic polyribosome aggregation. The most effective of these was alanine, whose effect of promoting polyribosomal aggregation was accompanied by a decrease in the polypeptide-chain elongation time. The following observations indicate that alanine plays an important physiological role in the regulation of hepatic protein synthesis. Alanine was the amino acid showing the largest decrease in hepatic content in the transition from high (fed) to low (starved) rates of protein synthesis. The administration of glucose or pyruvate is also effective in increasing liver protein synthesis in starved rats, and their effects were accompanied by an increased hepatic alanine content. An increase in hepatic ornithine content does not lead to an increased protein synthesis, unless it is accompanied by an increase of alanine. The effect of alanine is observed either in vivo, in rats pretreated with cycloserine to prevent its transamination, or in isolated liver cells under conditions in which its metabolic transformation is fully impeded.


1980 ◽  
Vol 186 (1) ◽  
pp. 35-45 ◽  
Author(s):  
A J Dickson ◽  
C I Pogson

Methods have been derived which permit the isolation of undergraded polyribosomes from isolated rat liver cells. Under the conditions used the polyribosome profile of hepatocytes immediately after isolation was essentially identical with that from intact liver. However, during incubation of cells in complex physiological media there was a progressive dissociation of polyribosomes. The addition of a variety of factors that produce reaggregation of polyribosomes in rat liver in vivo did not prevent dissociation during cell incubations. Although large polyribosomes were lost most rapidly, the albumin-synthesizing capacity of isolated cells was not selectively lost when compared with total protein synthesis. The significance of these results for the use of isolated hepatocytes in the study of liver protein synthesis is discussed.


1975 ◽  
Vol 26 (6) ◽  
pp. 1063
Author(s):  
LEA Symons ◽  
WO Jones

Incorporation of radioisotopically labelled L-leucine into skeletal muscle proteins was measured in vivo and in vitro, and into liver proteins in vivo in three groups of sheep: (1) infected by Trichostrongylus colubriformis, (2) uninfected, pair-fed with the infected animals, (3) uninfected, fed ad lib. Incorporation of [14C]L-leucine by an homogenate of wool follicles from infected and uninfected sheep was also measured. Incorporation of leucine by muscle, and hence muscle protein synthesis, was equally depressed in the anorexic infected sheep losing weight, and in pair-fed animals, whether measured in vivo or in vitro, or expressed in terms of either RNA or DNA. Incorporation into protein was elevated equally in vivo in the livers of the infected and pair-fed sheep when expressed in terms of content of tissue nitrogen, but not in terms of cither nucleic acid. Incorporation by the wool follicular homogenate was appreciably depressed by the infection and is consistent with the poor wool growth in nematode infections. These results show that the same depression of skeletal muscle and, possibly, elevation of liver protein synthesis occur in a ruminant as were reported earlier for laboratory monogastric animals with intestinal nematode infections. Pair-feeding uninfected animals in both this and the earlier experiments emphasized the importance of anorexia as a major cause of these effects on protein synthesis. The importance of these effects upon production is discussed briefly.


1989 ◽  
Vol 77 (6) ◽  
pp. 651-655 ◽  
Author(s):  
S. D. Heys ◽  
A. C. Norton ◽  
C. R. Dundas ◽  
O. Eremin ◽  
K. Ferguson ◽  
...  

1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 μg/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 μmol/100 g body weight) 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane.


1996 ◽  
Vol 75 (6) ◽  
pp. 853-865 ◽  
Author(s):  
S. Tesseraud ◽  
R. Peresson ◽  
J. Lopes ◽  
A.M. Chagneau

We analysed the respective influences of age and lysine deficiency on skeletal muscle and liver protein turnover. Growing male broilers were fed ad libirum on isoenergetic diets containing 2OO g crude protein/kg which varied in their lysine content (7·7 or 10·1 g/kg). Fractional rates of protein synthesis (FSR) were measured in vivo in the liver and the pectoralis major muscle of 2-, 3- and 4-week-old chickens (flooding dose of l-[143H]phenylalanine). Fractional rates of proteolysis (FBR) were estimated for the same tissues as the difference between synthesis and growth. Over the 2-week period liver FSR and FBR were unchanged, whereas muscle FSR decreased with age. This developmental decline was related to the lower capacity for protein synthesis (Cs) without any modifications of the translational efficiency. Whatever the age, lysine deficiency resulted in significant decreases in body weight, tissue protein content and tissue protein deposition, apparently because of reduced amounts of proteins synthesized. We recorded a difference in the response of the two tissues to lysine deficiency, the pectoralis major being more sensitive than the liver. When comparing birds of the same age, liver FSR and FBR were not modified by the diet, where as muscle FSR, Cs and FBR were higher in chicks fed on a lysinc-deficient diet than in the controls. Conversely, when chicks of similar weights were compared, the main effect of the dietary deficiency was an increase in muscle FBR. The results suggest that lysine deficiency not only delayed chick development so that protein turnover was affected, but also induced greater changes in metabolism. Thus, the principal mechanism whereby muscle mass decreased appeared to be a change in FBR.


1992 ◽  
Vol 1 (3) ◽  
pp. 37-56 ◽  
Author(s):  
Leonard Friedman ◽  
John Scalera ◽  
James E. Keys ◽  
Edmund L. Peters ◽  
Dennis W. Gaines ◽  
...  

The effects of 2-chioroethanol (2-CE) on rat tissue following in vitro and in vivo exposure were studied. At concentrations as low as 2.5 mg/ml, protein synthesis in liver slices was inhibited; at concentrations of 25 mg/ml and above, RNA synthesis and respiration were also impaired. Single oral doses of 2-CE to young adult rats at levels of 15-40 mg/kg body weight depressed liver nonprotein sulfhydryl (GSH) concentration and liver protein but not RNA synthesis. Liver lipid was increased by 7 hr after a single oral dose of 30 mg/kg. The time courses and dose-response relationship for GSH depletion and restoration and for protein synthesis inhibition and recovery were similar. The livers of female rats were more sensitive than the livers of male rats to the effects of 2-CE. Protein synthesis was also depressed in kidneys of 2-CE-treated male rats but at higher doses than those needed for this effect to occur in livers of the same animals. Liver polysome disaggregation also occurred after oral 2-CE doses of 20 mg/kg and greater. The effects of 2-CE on ribosome profiles and protein synthesis were at least partially reversed by concurrent intraperitoneal administration of cysteine. The possible relationship of these findings to a role of GSH in protein synthesis is discussed.


FEBS Letters ◽  
1973 ◽  
Vol 29 (3) ◽  
pp. 329-332 ◽  
Author(s):  
A. Sarasin ◽  
Y. Moulé ◽  
N. Darracq

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