scholarly journals The effects of salicylate on the activity of rat liver tyrosine–2-oxoglutarate aminotransferase in vitro and in vivo

1972 ◽  
Vol 126 (2) ◽  
pp. 347-350 ◽  
Author(s):  
A. A.-B. Badawy
Keyword(s):  
Rat Liver ◽  
Pyridoxal Phosphate ◽  
Actinomycin D ◽  
Sodium Salicylate ◽  
Intraperitoneal Administration ◽  
Tyrosine Aminotransferase ◽  
Major Effect ◽  
Endogenous Activity

1. Salicylate, in concentrations of 0.25mm and above, enhances the basal activity of tyrosine–2-oxoglutarate aminotransferase in homogenates of rat liver incubated in the absence of added pyridoxal 5′-phosphate (endogenous activity). The effect is decreased by increasing the concentration of the cofactor. 2. The intraperitoneal administration of sodium salicylate enhances the activity of rat liver tyrosine aminotransferase; the major effect during the first hour being on the enzyme in the absence of added pyridoxal phosphate. Actinomycin D prevents the induction of the enzyme by cortisol and tryptophan. Induction by pyridoxine or salicylate is 50% inhibited by actinomycin D. The effects of the injections of various combinations of cortisol, pyridoxine and salicylate were also studied in the absence or presence of actinomycin D. 3. It is suggested that salicylate induces rat liver tyrosine aminotransferase by displacing its protein-bound cofactor and that a cofactor-type induction of the hepatic enzyme occurs in pyridoxine-treated rats.

scholarly journals The effects of salicylate on the activity of rat liver tryptophan pyrrolase in vitro and in vivo

1971 ◽  
Vol 123 (2) ◽  
pp. 171-174 ◽  
Author(s):  
A. A.-B. Badawy ◽  
M. J. H. Smith
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Binding Sites ◽  
Actinomycin D ◽  
Sodium Salicylate ◽  
Progressive Increase ◽  
Tryptophan Pyrrolase ◽  
Enzyme Ratio

1. Salicylate, in concentrations of 0.05mm and above, inhibits the basal activity of tryptophan pyrrolase in homogenates of rat liver and the activity induced by cortisol but not that induced by tryptophan. The inhibition is abolished by adding haematin to the reaction mixtures. 2. The intraperitoneal injection of 400mg of sodium salicylate/kg in the rat causes a decrease in the tryptophan pyrrolase activity in the liver at 30min, the activity is restored to normal at 2h, increases to sixfold after 5h and returns to the basal value at 12h. The activation of the enzyme by salicylate is prevented by the administration of cycloheximide but not by pretreatment with actinomycin D. The effects of the combined injection of salicylate and cortisol are additive, whereas those of salicylate plus tryptophan are not. The injection of salicylate causes a progressive increase in the holo-/apo-enzyme ratio and an increased content of tryptophan in the liver over a period of 3h. 3. It is suggested that salicylate inhibits tryptophan pyrrolase activity in vitro and in vivo by interacting with iron protoporphyrins and causes a later enhancement of the enzyme activity in vivo by a mechanism involving the release of tryptophan from its binding sites on circulating albumin and on other proteins.

Effect of angiotensin II and sodium depletion on angiotensinogen production

1980 ◽  
Vol 238 (2) ◽  
pp. E145-E149 ◽  
Author(s):  
H. C. Herrmann ◽  
B. J. Morris ◽  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Actinomycin D ◽  
Ethinyl Estradiol ◽  
Intraperitoneal Administration ◽  
Plasma Renin ◽  
Sodium Depletion ◽  
Liver Slices ◽  
Plasma Angiotensin

An in vitro preparation of liver slices was used to study the effect of angiotensin II and sodium depletion on the synthesis of angiotensinogen in rats. Two other treatments known to increase plasma angiotensinogen concentration in vivo, viz., intraperitoneal administration of dexamethasone or ethinyl estradiol, resulted in an increase in the rate of release of angiotensinogen by liver slices; this increase was inhibited by adding actinomycin D or vincristine to the incubation medium. Intravenous infusion of angiotensin II (33 ng/min for 3 days) also produced a marked increase in the release of angiotensinogen concentration and a decrease in plasma renin activity. In contrast, no change in the rate of release of angiotensinogen was observed in rats depleted of sodium for 7--14 days, even though these animals exhibited a marked increase in plasma angiotensin II concentration. Plasma angiotensinogen concentration decreased by 30%, presumably as a consequence of the accompanying increase in renin secretion. These results provide further evidence that the synthesis of angiotensinogen may be increased by angiotensin II, but indicate that the circulating level of angiotensin II in sodium-deficient animals is not sufficiently high to produce this response.

scholarly journals dl-canaline and 5-fluoromethylornithine. Comparison of two inactivators of ornithine aminotransferase

1990 ◽  
Vol 268 (2) ◽  
pp. 409-414 ◽  
Author(s):  
F N Bolkenius ◽  
B Knödgen ◽  
N Seiler
Keyword(s):  
Rat Liver ◽  
Active Site ◽  
Absorption Maximum ◽  
Intraperitoneal Administration ◽  
Unsaturated Ketone ◽  
Ornithine Aminotransferase ◽  
Irreversible Inhibitor ◽  
Oxime Formation

5-Fluoromethylornithine (5FMOrn) is an enzyme-activated irreversible inhibitor or ornithine aminotransferase (L-ornithine:2-oxo-acid 5-aminotransferase, OAT). For purified rat liver OAT, Ki(app.) was found to be 30 microM. and tau 1/2 = 4 min. Of the four stereomers of 5FMOrn only one reacts with OAT. The formation of a chromophore with an absorption maximum at 458 nm after inactivation of OAT by 5FMOrn suggests the formation of an enamine intermediate, which is slowly hydrolysed to release an unsaturated ketone. L-Canaline [(S)-2-amino-4-amino-oxybutyric acid] is a well-known irreversible inhibitor of OAT. Not only the natural L-enantiomer but also the D-enantiomer reacts by oxime formation with pyridoxal 5′-phosphate in the active site of the enzyme, although considerably more slowly. This demonstrates that the stereochemistry at C-2 of ornithine is not absolutely stringent. In vitro, canaline reacted faster than 5FMOrn with OAT. In vivo, however, only incomplete OAT inhibition was observed with canaline. Whereas intraperitoneal administration of 10 mg of 5FMOrn/kg body wt. to mice was sufficient to inactivate OAT in brain and liver by 90% for 24 h, 500 mg of DL-canaline/kg body wt. only produced a transient inhibition of 65-70%. The accumulation of ornithine in these tissues was considerably slower and the maximum concentrations lower than were achieved with 5FMOrn. It appears that DL-canaline, in contrast with 5FMOrn, is not useful as a tool in studies of biological consequences of OAT inhibition.

scholarly journals Studies of the ethylation of rat liver transfer ribonucleic acid after administration of l-ethionine

1972 ◽  
Vol 128 (1) ◽  
pp. 59-68 ◽  
Author(s):  
A. E. Pegg
Keyword(s):  
Rat Liver ◽  
Ribonucleic Acid ◽  
Major Part ◽  
Actinomycin D ◽  
Major Product ◽  
The Other ◽  
Methyl Donor ◽  
Principal Product

1. The ethylated nucleosides present in tRNA isolated from the livers of rats treated with 0.5g of l-ethionine/kg body wt. were investigated. Evidence that this tRNA contained N2-ethylguanine, N2N2-diethylguanine, N2-ethyl-N2-methylguanine, 7-ethylguanine, two ethylated pyrimidines and ethylated ribose groups was obtained. 2. Ethylation of bacterial tRNA was catalysed by extracts containing tRNA methylases prepared from rat liver by using S-adenosyl-l-ethionine as an ethyl donor, but the rate of ethylation was 20 times less than the rate of methylation with S-adenosyl-l-methionine as a methyl donor. 3. The principal product of such ethylation in vitro was N2-ethylguanine and traces of the other ethylated guanines and pyrimidines found in tRNA isolated from rats treated with ethionine in vivo were also found. 1-Ethyladenine was not formed, although 1-methyl-adenine is a major product of methylation of bacterial tRNA by these extracts, and 1-ethyladenine was not present in the rat liver tRNA isolated from ethionine-treated animals. 4. After injection of actinomycin D (15mg/kg body wt.) or l-methionine (1.0g/kg body wt.) before the ethionine, ethylation of tRNA was diminished by about 80% but not completely abolished. Administration of 1-aminocyclopentanecarboxylic acid (2.5g/kg body wt.) to inhibit the formation of S-adenosyl-l-ethionine inhibited ethylation of tRNA by 44%. 5. These results suggest that not all of the ethylation of tRNA that occurs in the livers of rats treated with ethionine is mediated by the action of tRNA methylases acting with S-adenosyl-l-ethionine as a substrate, but that this pathway does occur and accounts for a major part of the observed ethylation. 6. The results are discussed with reference to ethionine-induced hepatocarcinogenesis.

scholarly journals Stabilization of rat liver tyrosine aminotransferase by tetracycline

1975 ◽  
Vol 150 (3) ◽  
pp. 329-333 ◽  
Author(s):  
R Hannah ◽  
M K Sahib
Keyword(s):  
Rat Liver ◽  
De Novo ◽  
Rabbit Antiserum ◽  
Tyrosine Aminotransferase ◽  
Enzyme Inactivation ◽  
Aminotransferase Activity ◽  
Rapid Inactivation ◽  
Liver Homogenates

Rat liver tyrosine aminotransferase was purified 200-fold and an antiserum raised against it in rabbits. 2. Hepatic tyrosine aminotransferase activity was increased fourfold by tyrosine, twofold by tetracycline, 2.5-fold by cortisone 21-acetate and ninefold by a combination of tyrosine and cortisol administered intraperitoneally to rats. 3. Radioimmunoassay with 14C-labelled tyrosine aminotransferase, in conjunction with rabbit antiserum against the enzyme, revealed that cortisol stimulates the synthesis of the enzyme de novo, but that tetracycline has no such effect. 4. Incubation of rat liver homogenates with purified tyrosine aminotransferase in vitro leads to a rapid inactivation of the enzyme, which tetracycline partially inhibits. 5. The inactivation is brought about by intact lysosomes, and the addition of 10mM-cysteine increases the rate of enzyme inactivation, which is further markedly increased by 10mM-Mg2+ and 10mM-ATP. Here again tetracycline partially inhibits the decay rate, leading to the inference that the increase of tyrosine aminotransferase activity in vivo by tetracycline is brought about by the latter inhibiting the lysosomal catheptic action.

Effect of X-irradiation on gene expression of rat liver chemokines: in vivo and in vitro studies

2008 ◽  
Vol 46 (01) ◽  
Author(s):  
F Moriconi ◽  
H Christiansen ◽  
H Christiansen ◽  
N Sheikh ◽  
J Dudas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
In Vitro Studies ◽  
X Irradiation

CONTRIBUTION TO THE EXISTENCE OF REGULATORY MECHANISMS AT THE ADRENAL LEVEL

1972 ◽  
Vol 70 (4) ◽  
pp. 741-757
Author(s):  
Otto Linèt
Keyword(s):  
Orotic Acid ◽  
Adrenal Glands ◽  
Actinomycin D ◽  
Delay Period ◽  
Regulatory Mechanisms ◽  
Leucine Incorporation ◽  
Total Period ◽  
Free Media

ABSTRACT Rat adrenal glands atrophied by the administration of cortisol acetate in vivo were used as a model for the study of early metabolic processes occurring in vitro. Atrophied adrenals incubated in the presence of 14C-leucine incorporated subnormal quantities of this amino acid per mg of protein for the first 120 min. When the incubation lasted for a total period of 180 or 240 min a supranormal rise in the 14C-leucine incorporation was observed. Similar changes occurred with some delay with regard to corticosterone production as expressed per 100 mg of tissue. No differences in 14C-leucine incorporation were observed between the control and atrophied adrenals in vivo. Homogenates from atrophied glands incorporated 14C-leucine to a greater extent than the control homogenates. The in vitro incorporation of 14C-orotic acid into the RNA was also higher in atrophied adrenals. The in vitro use of actinomycin D, cycloheximide and amphenone indicated that corticosterone production depended on the incorporation of 14C-leucine. The addition of cortisol to the incubation media markedly decreased the enhancement of 14C-lysine incorporation into the protein of atrophied adrenals. These, as well as additional results suggest rebound phenomena: once atrophic adrenals are transferred to cortisol-free media, reparative processes begin after a delay period. Such phenomena seem to be mediated by regulatory mechanisms at the adrenal level.

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