scholarly journals Inhibition of protein synthesis by N-methyl-N-nitrosourea in vivo

1973 ◽  
Vol 136 (2) ◽  
pp. 303-309 ◽  
Author(s):  
P. Kleihues ◽  
P. N. Magee
Keyword(s):  
Protein Synthesis ◽  
Direct Consequence ◽  
Maximum Effect ◽  
Adult Rat ◽  
Mechanism Of Inhibition ◽  
Weanling Rats ◽  
Inhibition Of Protein Synthesis ◽  
Hepatic Protein Synthesis

1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2–3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyribosomes was found in adult rat brains although N-methyl-N-nitrosourea inhibited cerebral and hepatic protein synthesis to a similar extent. In weanling rats N-methyl-N-nitrosourea caused a shift in the cerebral polyribosome profile similar to but less marked than that in rat liver. 3. Reaction of polyribosomal RNA with N-[14C]methyl-N-nitrosourea in vitro did not lead to a disaggregation of polyribosomes although the amounts of 7-methylguanine produced were up to twenty times higher than those found after administration of sublethal doses in vivo. 4. It was concluded that changes in the polyribosome profile induced by N-methyl-N-nitrosourea may reflect the mechanism of inhibition of protein synthesis rather than being a direct consequence of the methylation of polyribosomal mRNA.

scholarly journals A possible mechanism of inhibition of protein synthesis by dimethylnitrosamine

1967 ◽  
Vol 105 (2) ◽  
pp. 625-631 ◽  
Author(s):  
S. Villa-Treviño
Keyword(s):  
Protein Synthesis ◽  
Messenger Rna ◽  
Transfer Rna ◽  
The State ◽  
Leucine Incorporation ◽  
Mechanism Of Inhibition ◽  
Nuclear Rna ◽  
Inhibition Of Protein Synthesis ◽  
Hepatic Protein Synthesis

1. The incorporation of [14C]leucine into liver proteins of rats was measured in vivo at various times after treatment of the animals with dimethylnitrosamine and was correlated with the state of the liver ribosomal aggregates. Inhibition of incorporation ran parallel with breakdown of the aggregates. 2. Inhibition of leucine incorporation into protein and breakdown of ribosomal aggregates were not preceded by inhibition of incorporation of [14C]orotate into nuclear RNA of the liver. 3. Evidence was obtained of methylation of nuclear RNA in the livers of rats treated with [14C]dimethylnitrosamine. 4. Zonal centrifugation analysis of radioactive, nuclear, ribosomal and transfer RNA from livers of rats treated with [14C]dimethylnitrosamine revealed labelling of all centrifugal fractions to about the same extent. 5. It is suggested that methylation of messenger RNA might occur in the livers of dimethylnitrosamine-treated rats and the possible relation of this to inhibition of hepatic protein synthesis is discussed.

Comparison of hepatic protein synthesis in vivo versus in vitro in the tumor-bearing rat

1987 ◽  
Vol 42 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Robert S. Warren ◽  
M. Jeevanandam ◽  
Murray F. Brennan
Keyword(s):  
Protein Synthesis ◽  
Tumor Bearing ◽  
Hepatic Protein Synthesis

Effects of liver ischemia on hepatic protein synthesis in vitro and in vivo

1982 ◽  
Vol 114 (1) ◽  
pp. 143-148 ◽  
Author(s):  
PER-OLOF HASSELGREN ◽  
JÖRGEN FORNANDER ◽  
RUDOLF JAGENBURG ◽  
ELISABETH SUNDSTRÖM
Keyword(s):  
Protein Synthesis ◽  
Liver Ischemia ◽  
Hepatic Protein Synthesis

scholarly journals Inhibition of protein synthesis by glucagon in different rat muscles and protein fractions in vivo and in the perfused rat hemicorpus

1988 ◽  
Vol 251 (3) ◽  
pp. 727-732 ◽  
Author(s):  
V R Preedy ◽  
P J Garlick
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Plasma Concentrations ◽  
Type I ◽  
Inhibition Of Protein Synthesis ◽  
Fasted Rats ◽  
Mixed Protein

The effect of glucagon on the rate of muscle protein synthesis was examined in vivo and in the isolated perfused rat hemicorpus. An inhibition of protein synthesis in skeletal muscles from overnight-fasted rats at various plasma concentrations of glucagon was demonstrated in vivo. The plantaris muscle (Type II, fibre-rich) was more sensitive than the soleus (Type I, fibre-rich). Myofibrillar and sarcoplasmic proteins were equally sensitive in vivo. However, protein synthesis in mixed protein and in sarcoplasmic and myofibrillar fractions of the heart was unresponsive to glucagon in vivo. In isolated perfused muscle preparations from fed animals, the addition of glucagon also decreased the synthesis of mixed muscle proteins in gastrocnemius (Type I and II fibres) and plantaris, but not in the soleus. The sarcoplasmic and myofibrillar fractions of the plantaris were also equally affected in vitro. Similar results were observed in vitro with 1-day-starved rats, but the changes were less marked.

Acute inhibition of rat heart protein synthesis in vitro during beta-adrenergic stimulation or hypoxia

1988 ◽  
Vol 255 (4) ◽  
pp. E537-E547 ◽  
Author(s):  
S. J. Fuller ◽  
P. H. Sugden
Keyword(s):  
Protein Synthesis ◽  
Rat Heart ◽  
Energy Status ◽  
Adrenergic Stimulation ◽  
Lactate Output ◽  
Inhibition Of Protein Synthesis ◽  
Cardiac Energy ◽  
Stimulation Of

In the anterogradely perfused rat heart with glucose as fuel, 1 microM isoproterenol (ISO) inhibited the insulin (INS) plus adenosine deaminase (AdoDA) stimulation of ventricular protein synthesis by 72%. ISO (1 microM) alone had no effect on ventricular protein synthesis but inhibited atrial protein synthesis by 20%. The concentration dependence of the ISO inhibition was similar to the stimulation of glucose uptake by ISO. Inhibition could not be overcome by increasing INS concentrations. The effects of ISO were diminished by propranolol and could be partially mimicked by forskolin (FSK) or 8-(4-chlorophenylthio-)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). The stimulation of protein synthesis by noncarbohydrate fuels was antagonized by ISO. Hypoxia (PO2 = 50%) also antagonized the INS stimulation of ventricular protein synthesis but did not affect basal rates. ATP contents were decreased by ISO but not by a PO2 of 50%. Both manipulations increased lactate output. The inhibition of protein synthesis by ISO could possibly be explained by indirect effects of ISO on cardiac "energy status." Furthermore, inhibition may thus represent purely an in vitro phenomenon and may not occur in vivo. However, the possibility that there are more direct effects of ISO on the machinery of protein synthesis has not been excluded. The inhibition of protein synthesis by hypoxia cannot be explained by changes in energy status and may result from intracellular lactoacidosis.

Contrasting effects of protein synthesis inhibition and of cyclic AMP on apoptosis in the developing retina

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1439-1448
Author(s):  
S.K. Rehen ◽  
M.H. Varella ◽  
F.G. Freitas ◽  
M.O. Moraes ◽  
R. Linden
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Neuron Death ◽  
Inhibition Of Protein Synthesis ◽  
Retinal Explants ◽  
Induced Apoptosis

The role of protein synthesis in apoptosis was investigated in the retina of developing rats. In the neonatal retina, a ganglion cell layer, containing neurons with long, centrally projecting axons, is separated from an immature neuroblastic layer by a plexiform layer. This trilaminar pattern subsequently evolves to five alternating cell and plexiform layers that constitute the mature retina and a wave of programmed neuron death sweeps through the layers. Apoptosis due to axon damage was found in ganglion cells of retinal explants within 2 days in vitro and was prevented by inhibition of protein synthesis. Simultaneously, protein synthesis blockade induced apoptosis among the undamaged cells of the neuroblastic layer, which could be selectively prevented by an increase in intracellular cyclic AMP. Both the prevention and the induction of apoptosis among ganglion cells or neuroblastic cells, respectively, occurred after inhibition of protein synthesis in vivo. The results show the coexistence of two mechanisms of apoptosis within the organized retinal tissue. One mechanism is triggered in ganglion cells by direct damage and depends on the synthesis of proteins acting as positive modulators of apoptosis. A distinct, latent mechanism is found among immature neuroblasts and may be repressed by continuously synthesized negative modulators, or by an increase in intracellular cyclic AMP.

scholarly journals Biochemical studies with a new cytotoxic immunosuppressive agent, 3-acetyl-5-(4-fluorobenzylidene)-2,5-dihydro-4-hydroxy-2-oxothiophen (I.C.I. 47776)

1967 ◽  
Vol 102 (3) ◽  
pp. 705-711 ◽  
Author(s):  
T. J. Franklin ◽  
B. Higginson
Keyword(s):  
Protein Synthesis ◽  
Lymph Node ◽  
Nucleic Acid ◽  
Acid Synthesis ◽  
Nucleic Acid Synthesis ◽  
Atp Concentration ◽  
Inhibition Of Protein Synthesis ◽  
Lymph Node Cells

1. A new cytotoxic agent, 3-acetyl-5-(4-fluorobenzylidene)-2,5-dihydro-4-hydroxy-2-oxothiophen (I.C.I. 47776), strongly inhibits protein and nucleic acid synthesis and, to a smaller extent, respiration in lymph-node cells and Landschütz ascites-tumour cells in vitro. 2. The activity of I.C.I. 47776 in vitro declines as the pH of the medium is increased and is inversely proportional to the concentration of serum in the medium. 3. The compound has no effect on the incorporation of leucine by a cell-free preparation from Landschütz ascites cells containing ATP and phosphoenolpyruvate. 4. I.C.I. 47776 stimulates glycolysis in suspensions of Landschütz ascites cells in the presence of excess of glucose but has no effect on glycolysis in suspensions of rat lymph-node cells. 5. I.C.I. 47776 markedly depresses ATP concentration in ascites cells in the absence of glucose but has no effect on the ATP concentration in the presence of glucose. The inhibition of protein synthesis by I.C.I. 47776 in ascites cells is, however, only partially reversed by the addition of glucose. 6. The ATP concentration of rat lymph-node cells incubated with I.C.I. 47776 in the absence of glucose is also markedly depressed but the addition of glucose increases the ATP concentration only slightly. Further, glucose has no effect on the inhibition of protein synthesis in lymph-node cells by I.C.I. 47776. 7. It is suggested that I.C.I. 47776 inhibits protein and nucleic acid synthesis in cell suspensions indirectly by acting as a mitochondrial poison. 8. The relevance of studies on the activity of I.C.I. 47776 in vitro to its cytotoxic and immunosuppressive action in vivo is discussed.

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