scholarly journals The oxidation of leucine in tumour-bearing rats

1990 ◽  
Vol 268 (1) ◽  
pp. 241-244 ◽  
Author(s):  
J M Argilés ◽  
F J López-Soriano
Keyword(s):  
Amino Acid ◽  
Time Course ◽  
Similar Rate ◽  
Turnover Rates ◽  
Tissue Slices ◽  
Tracer Dose ◽  
Tumour Bearing ◽  
Walker 256 ◽  
14Co2 Release

Rats bearing the Walker-256 carcinosarcoma showed significant changes in leucine metabolism compared with their non-tumour-bearing controls. After a single intravenous tracer dose of L-[1-14C]leucine in vivo, 14CO2 release by tumour-bearing rats was significantly elevated throughout the time course of administration. In addition, both the clearance and turnover rates of the tracer were significantly enhanced in these animals. Incubation of soleus muscles from control and tumour-bearing rats in the presence of L-[1-14C]leucine revealed an enhanced oxidation of the amino acid in the tumour-bearing group. Tumour tissue slices were also able to oxidize the tracer at a similar rate to that found in soleus muscles from control animals.

scholarly journals A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 404
Author(s):  
Gabriela de Matuoka e Chiocchetti ◽  
Leisa Lopes-Aguiar ◽  
Natália Angelo da Silva Miyaguti ◽  
Lais Rosa Viana ◽  
Carla de Moraes Salgado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Cancer Cachexia ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256 ◽  
Muscle Changes ◽  
The Right ◽  
Biomarker Research ◽  
Host Metabolism

Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed 1H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host’s age, highlighting the need to adopting the right animal age when studying cancer cachexia.

scholarly journals A New Technic for the Production of an in Vivo Labeled Fibrinogen

Blood ◽  
1967 ◽  
Vol 29 (4) ◽  
pp. 517-525 ◽  
Author(s):  
HENRY GANS ◽  
JAMES MC LEOD ◽  
JAMES T. LOWMAN
Keyword(s):  
Amino Acid ◽  
Specific Activity ◽  
High Specific Activity ◽  
Entire Period ◽  
Turnover Rates ◽  
Prolonged Infusion ◽  
Slow Infusion

Abstract The fact that in vitro labeled proteins, as a rule, exhibit faster turnover rates than in vivo labeled materials led us to explore means of obtaining in vivo labeled fibrinogen of high specific activity. It was found that defibrination of the rat provides a stimulus for the liver to regenerate fibrinogen at an accelerated rate. Administration of seleno75 methionine shortly after thrombin-induced defibrination of the animal resulted in the incorporation of large quantities of the label. The rate of incorporation was further increased if the amino acid was administered as a slow infusion during the entire period of fibrinogen regeneration. In addition, prior nephrectomy of the animal would appear to result in a slight increase in specific activity of the fibrinogen preparation obtained. The results of these studies indicate that defibrination, nephrectomy, and the prolonged infusion of the labeled amino acid selenomethionine provided us with a technic for obtaining a biosynthetically labeled, γ-emitting, fibrinogen preparation of high specific activity.

scholarly journals Potent Antibody-Mediated Neutralization and Evolution of Antigenic Escape Variants of Simian Immunodeficiency Virus Strain SIVmac239 In Vivo

2008 ◽  
Vol 82 (19) ◽  
pp. 9739-9752 ◽  
Author(s):  
Shuji Sato ◽  
Eloisa Yuste ◽  
William A. Lauer ◽  
Eun Hyuk Chang ◽  
Jennifer S. Morgan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Time Course ◽  
Neutralizing Antibody ◽  
Synonymous Substitution ◽  
Viral Envelope ◽  
Single Amino Acid ◽  
Nucleotide Substitutions ◽  
Recombinant Viruses ◽  
Synonymous Substitution Rates

ABSTRACT Here, we describe the evolution of antigenic escape variants in a rhesus macaque that developed unusually high neutralizing antibody titers to SIVmac239. By 42 weeks postinfection, 50% neutralization of SIVmac239 was achieved with plasma dilutions of 1:1,000. Testing of purified immunoglobulin confirmed that the neutralizing activity was antibody mediated. Despite the potency of the neutralizing antibody response, the animal displayed a typical viral load profile and progressed to terminal AIDS with a normal time course. Viral envelope sequences from week 16 and week 42 plasma contained an excess of nonsynonymous substitutions, predominantly in V1 and V4, including individual sites with ratios of nonsynonymous to synonymous substitution rates (dN/dS) highly suggestive of strong positive selection. Recombinant viruses encoding envelope sequences isolated from these time points remained resistant to neutralization by all longitudinal plasma samples, revealing the failure of the animal to mount secondary responses to the escaped variants. Substitutions at two sites with significant dN/dS values, one in V1 and one in V4, were independently sufficient to confer nearly complete resistance to neutralization. Substitutions at three additional sites, one in V4 and two in gp41, conferred moderate to high levels of resistance when tested individually. All the amino acid changes leading to escape resulted from single nucleotide substitutions. The observation that antigenic escape resulted from individual, single amino acid replacements at sites well separated in current structural models of Env indicates that the virus can utilize multiple independent pathways to rapidly achieve similar levels of resistance.

scholarly journals Precise Estimation of In Vivo Protein Turnover Rates

2020 ◽  
Author(s):  
Jonathon J. O’Brien ◽  
Vikram Narayan ◽  
Yao Wong ◽  
Phillip Seitzer ◽  
Celeste M. Sandoval ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Turnover ◽  
Search Algorithm ◽  
Deuterium Oxide ◽  
Isotopic Labeling ◽  
Analytical Framework ◽  
Turnover Rates ◽  
Ion Distribution ◽  
Common Technique

AbstractIsotopic labeling with deuterium oxide (D2O) is a common technique for estimating in vivo protein turnover, but its use has been limited by two long-standing problems: (1) identifying non-monoisotopic peptides; and (2) estimating protein turnover rates in the presence of dynamic amino acid enrichment. In this paper, we present a novel experimental and analytical framework for solving these two problems. Peptides with high probabilities of labeling in many amino acids present fragmentation spectra that frequently do not match the theoretical spectra used in standard identification algorithms. We resolve this difficulty using a modified search algorithm we call Conditional Ion Distribution Search (CIDS). Increased identifications from CIDS along with direct measurement of amino acid enrichment and statistical modeling that accounts for heterogeneous information across peptides, dramatically improves the accuracy and precision of half-life estimates. We benchmark the approach in cells, where near-complete labeling is possible, and conduct an in vivo experiment revealing, for the first time, differences in protein turnover between mice and naked mole-rats commensurate with their disparate longevity.

Kinetic analysis of histone acetylation turnover and Trichostatin A induced hyper- and hypoacetylation in alfalfa

2002 ◽  
Vol 80 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Jakob H Waterborg ◽  
Tamás Kapros
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Similar Rate ◽  
Lysine Methylation ◽  
Histone H2a ◽  
Turnover Rates

Dynamic histone acetylation is a characteristic of chromatin transcription. The first estimates for the rate of acetylation turnover of plants are reported, measured in alfalfa cells by pulse, pulse-chase, and steady-state acetylation labeling. Acetylation turnover half-lives of about 0.5 h were observed by all methods used for histones H3, H4, and H2B. This is consistent with the rate at which changes in gene expression occur in plants. Treatment with histone deacetylase inhibitor Trichostatin A (TSA) induced hyperacetylation at a similar rate. Replacement histone variant H3.2, preferentially localized in highly acetylated chromatin, displayed faster acetyl turnover. Histone H2A with a low level of acetylation was not subject to rapid turnover or hyperacetylation. Patterns of acetate labeling revealed fundamental differences between histone H3 versus histones H4 and H2B. In H3, acetylation of all molecules, limited by lysine methylation, had similar rates, independent of the level of lysine acetylation. Acetylation of histones H4 and H2B was seen in only a fraction of all molecules and involved multiacetylation. Acetylation turnover rates increased from mono- to penta- and hexaacetylated forms, respectively. TSA was an effective inhibitor of alfalfa histone deacetylases in vivo and caused a doubling in steady-state acetylation levels by 4–6 h after addition. However, hyperacetylation was transient due to loss of TSA inhibition. TSA-induced overexpression of cellular deacetylase activity produced hypoacetylation by 18 h treatment with enhanced acetate turnover labeling of alfalfa histones. Thus, application of TSA to change gene expression in vivo in plants may have unexpected consequences.

Synthesis and Properties of "Hormonogene" and "Inhibitorogene" Type Oxytocin Analogs

1992 ◽  
Vol 57 (6) ◽  
pp. 1345-1351 ◽  
Author(s):  
B. C. Pal ◽  
Jiřina Slaninová ◽  
Tomislav Barth ◽  
Jerzy Trojnar ◽  
Michal Lebl
Keyword(s):  
Amino Acid ◽  
Inhibitory Action ◽  
Time Course ◽  
Solid Phase ◽  
Prolonged Time ◽  
Prolonged Effect ◽  
In Vivo Tests

Nα-Glycyl, diglycyl and triglycyl [2-D and [2-L-p-ethylphenylalanine]oxytocin analogs were synthesized by the solid phase technology utilizing racemic p-ethylphenylalanine. Analogs containing this amino acid of D-configuration were shown to be weak uterotonic antagonists both in vitro and in vivo tests; the compound containing triglycyl residue in position 1 was shown to have prolonged time course of inhibitory action. Analogs containing the L-amino acid were shown to be inhibitors of uterotonic activity of oxytocin in vitro, but uterotonic agonists with prolonged effect in vivo.

scholarly journals Mechanisms of replenishment of nuclear and rogen receptor in rat ventral prostate

1978 ◽  
Vol 174 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Edward Van Doorn ◽  
Nicholas Bruchovsky
Keyword(s):  
Androgen Receptor ◽  
Cell Division ◽  
Nuclear Receptor ◽  
Time Course ◽  
Ventral Prostate ◽  
Tissue Slices ◽  
Rat Ventral Prostate ◽  
Prostatic Cell

1. The concentration of androgen receptor in the nucleus of the prostatic cell is rapidly elevated by the administration in vivo of 2μg of [3H]testosterone to 1-day-castrated rats. From a concentration of 2300 receptors/nucleus at 5min after intravenous injection of hormone, there is an increase to 21000 receptors/nucleus at 60min. At the same time, the amount of binding of androgen in the cytoplasm remains constant at a relatively low value. 2. An identical dose of [3H]testosterone administered to 7-day-castrated rats produces a much smaller change in the concentration of nuclear receptor, from 700 receptors/nucleus at 5min to only 4300 receptors/nucleus at 60min. Thus the reservoir from which nuclear receptor is replenished is considerably smaller in regressed prostatic cells. Again, the amount of binding of androgen in the cytoplasm remains unchanged at a low value over the experimental time course of 60min. 3. In contrast with the scant labelling of cytoplasmic receptor achieved by injecting animals with [3H]testosterone, labelling in vitro, by incubation of tissue slices with radioisotope, indicates that prostate of 1-day-castrated animals actually contains 21400 receptors/cell in the cytoplasmic compartment, and prostate of 7-day-castrated animals 3000 receptors/cell. 4. Owing to the similarity between the concentration of nuclear receptor measured in vivo and the concentration of cytoplasmic receptor measured in vitro, the labelling techniques in vivo and in vitro were used in sequence to demonstrate the movement of most of the cytoplasmic receptor into the nucleus. In the 5–60min interval after the administration of [3H]testosterone to 1-day-castrated rats, a decrease of 17400 receptor molecules in the cytoplasm is exactly mirrored by an increase of 17200 receptor molecules in the nucleus. 5. These results imply that, in prostate of 1-day-castrated rats, nuclear receptor is replenished exclusively by translocation of cytoplasmic receptor. However, in the regressed prostate of 7-day-castrated rats, only about 25% of the nuclear receptor is replenished through translocation of existing cytoplasmic receptor. The remainder is ultimately synthesized during new rounds of cell division induced by hormone.

Plasma amino acid turnover rates and pools in rabbits: in vivo studies using stable isotopes.

1979 ◽  
Vol 237 (5) ◽  
pp. E418 ◽  
Author(s):  
I Nissim ◽  
A Lapidot
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
In Vivo Studies ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Plasma Amino Acids ◽  
Isotope Enrichment ◽  
Time Decay ◽  
Turnover Rates

Gas chromatography--mass spectrometry of plasma amino acids has been used to determine the 15N enrichments of plasma glycine and alanine in rabbits in different metabolic states. Isotope-enrichment time-decay curves of plasma amino acids were linear over the course of the measurements after intravenous administration of a single dose of 15N-amino acid. Glycine and alanine pools and turnover rate constants were estimated from decay data. The effects of diurnal variation and fasting on glycine and alanine pool sizes, turnover rates, and flux in rabbits were studied to provide information on the effect of metabolic stress on amino acid kinetics in the whole body. The observations suggests that the transport of systemic glycine or alanine into the hepatocyte is under the control of a regulatory mechanism that compensates for decrease in the extracellular levels of the amino acids by enhancing the activity of the transport system. The volumes of the glycine and alanine pools were found to correspond to the extracellular space of rabbits, and the glycine and alanine pools can be identified as extracellular. We conclude that the plasma glycine and alanine 15N isotope-enrichment time-decay curves over the 1st h after a single intravenous dose of the amino acid represent mainly the hepatic uptake of glycine and alanine from the extracellular pool.

scholarly journals Glutamine as a major nitrogen carrier to the liver in suckling rat pups

1988 ◽  
Vol 256 (2) ◽  
pp. 377-381 ◽  
Author(s):  
J Casado ◽  
A Felipe ◽  
M Pastor-Anglada ◽  
X Remesar
Keyword(s):  
Amino Acid ◽  
Glutamine Synthetase ◽  
Time Course ◽  
Membrane Vesicles ◽  
Hepatic Veins ◽  
Plasma Membrane Vesicles ◽  
Adult Rats ◽  
Suckling Rats ◽  
Rat Pups

We measured the amino acid concentrations in the afferent and efferent vessels of the liver in anaesthetized fed adult rats and in fed suckling rat pups. A much higher content of glutamine in the portal vein and the aorta than in hepatic veins suggests that this amino acid is actively taken up by the liver of fed suckling rat pups, conversely to what is found in adult rats. In an attempt to characterize further the mechanism(s) contributing to this enhanced glutamine uptake, we monitored the time course of 1 mM-glutamine transport into plasma-membrane vesicles purified from the livers of either adult or suckling rats. The concentrative Na+-dependent uptake of glutamine was lower in those vesicles obtained from pups than in those obtained from adult rats. Glutaminase and glutamine synthetase activities in livers from both experimental groups were also measured. Glutaminase and glutamine synthetase activities in suckling rats were about 3-fold higher and 2-fold lower respectively than those in adult rats. It is concluded that glutamine is a main nitrogen carrier to the liver in fed suckling rats. A high availability of this amino acid and an enzyme imbalance between glutamine-synthesizing and -degrading activities may account for the net uptake found in vivo.

scholarly journals Biosynthesis of Rat serum albumin

1971 ◽  
Vol 123 (4) ◽  
pp. 649-655 ◽  
Author(s):  
J. D. Judah ◽  
Marion R. Nicholls
Keyword(s):  
Amino Acid ◽  
Serum Albumin ◽  
Time Course ◽  
Time Lag ◽  
Rat Serum ◽  
Albumin Content ◽  
Double Label ◽  
Rat Serum Albumin

1. The labelling of intracellular and extracellular serum albumin was studied in liver slices and in whole rats by using new methods for the purification of the protein. 2. The results suggest that a polypeptide precursor is formed that is converted relatively slowly into serum albumin. 3. The effect of liver cell K+has been examined by a double-label method and it is shown that K+accelerates the rate of conversion of ‘precursor’ into albumin. The rate of transit of albumin across the cell membrane appears to be unrelated to the concentration of K+within the cell. 4. The time-course of incorporation of radioactive amino acid into albumin follows a sigmoidal mode. There is a pronounced time-lag before label starts to appear in intracellular albumin, and a further time-lag before it appears in extracellular albumin. 5. In slices the sum of intra- and extra-cellular label rises steadily from 30min after the start of labelling with a pulse of labelled leucine or valine and continues to rise for at least another 60min. This occurs whether labelling is stopped by addition of excess of carrier amino acid or with cycloheximide (100μm) or both. 6. The intracellular albumin content remains constant whether slices are maintained with low or normal intracellular K+concentrations. 7. Specific radioactivities of intracellular albumin (and fractions thereof) and of extracellular albumin were determined in vitro and in vivo. The results show that the intracellular albumin cannot be a precursor of extracellular albumin, unless a very small compartment is turning over much more rapidly than the bulk of the liver albumin or even of the microsomal albumin.

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