Effects of glucocorticoid treatment on cardiac protein synthesis and degradation

1986 ◽  
Vol 250 (6) ◽  
pp. C821-C827 ◽  
Author(s):  
A. F. Clark ◽  
G. N. DeMartino ◽  
K. Wildenthal
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Lower Body ◽  
Glucocorticoid Treatment ◽  
Body Weights ◽  
Langendorff Perfusion ◽  
Perfused Hearts ◽  
Fasted Rats ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

We treated rats with dexamethasone (DEX, 1 mg . kg-1 . day-1) and examined the effects of this glucocorticoid on heart protein metabolism using atrial explant and Langendorff perfusion preparations. Fasted rats treated with DEX for 2 days had significantly lower body weights (92% of control, P less than 0.001) and larger hearts (106% of control, P less than 0.005) than fasted control animals. Protein and RNA concentrations remained constant. In atrial explants, DEX treatment produced a 19% increase in protein synthesis (P less than 0.001) and a 13% increase in protein degradation (P less than 0.002). In Langendorff-perfused hearts, DEX treatment caused a 36% increase in protein synthesis (P less than 0.02), while protein degradation was 8% above control (P greater than 0.05). Thus, in contrast to their catabolic effects on skeletal muscle, glucocorticoids are anabolic on the heart. The increased accumulation of total cardiac protein during early glucocorticoid administration is mediated entirely via increased rates of synthesis.

scholarly journals Comparison of protein synthesis and degradation in incubated and perfused muscle

1983 ◽  
Vol 212 (3) ◽  
pp. 649-653 ◽  
Author(s):  
A S Clark ◽  
W E Mitch
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Insulin Treatment ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Protein Degradation ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Rates of muscle protein synthesis and degradation measured in the perfused hindquarter were compared with those in incubated epitrochlearis muscles. With fed or starved mature rats, results without insulin treatment were identical. With insulin treatment, protein synthesis in perfused hindquarters was greater, though protein degradation was the same. Thus rates of muscle protein degradation estimated by these two methods in vitro correspond closely.

scholarly journals The effect of insulin and intermittent mechanical stretching on rates of protein synthesis and degradation in isolated rabbit muscle

1985 ◽  
Vol 230 (1) ◽  
pp. 117-123 ◽  
Author(s):  
R M Palmer ◽  
P A Bain ◽  
P J Reeds
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Suppressive Effect ◽  
Rabbit Muscle ◽  
Degradation Rates ◽  
Forelimb Muscles ◽  
Amino Acid Balance ◽  
Mechanical Stretching ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Tyrosine balance and protein synthesis were studied during the same incubation in isolated rabbit forelimb muscles. From these measurements, protein degradation was calculated. Isolated muscles were usually in a state of negative amino acid balance, principally as a result of the 75% decrease in protein synthesis. Muscles from rabbits starved for 18 h had lower rates of both protein synthesis and degradation compared with muscles from normally fed rabbits. Intermittent mechanical stretching and the addition of insulin at 100 microunits/ml increased rates of both protein synthesis and degradation. Increases in the rate of protein synthesis were proportionately greater in the muscles from starved animals. In muscles from both fed and starved donors, increases in protein-synthesis rates owing to intermittent stretching and insulin were proportionately greater than the increases in degradation rates. For example, insulin increased the rate of protein synthesis in the muscles from starved donors by 111% and the rate of degradation by 31%. Insulin also increased the rate of protein synthesis when added at a higher concentration (100 munits/ml); at this concentration, however, the rate of protein degradation was not increased. The suppressive effect of insulin on high rates of protein degradation in other skeletal-muscle preparations may reflect a non-physiological action of the hormone.

scholarly journals The effects of cutting or of stretching skeletal muscle in vitro on the rates of protein synthesis and degradation

1980 ◽  
Vol 188 (1) ◽  
pp. 247-254 ◽  
Author(s):  
M J Seider ◽  
R Kapp ◽  
C P Chen ◽  
F W Booth
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Extensor Digitorum Longus ◽  
High Energy ◽  
Extensor Digitorum ◽  
Muscle Fibres ◽  
High Energy Phosphates ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Rates of protein synthesis were significantly lower in the cut soleus and extensor digitorum longus muscles than in their uncut counterparts. Rates of protein degradation were significantly higher in cut soleus muscles, but not in cut extensor digitorum longus muscles as compared with their uncut controls. Concentrations of ATP and phosphocreatine were significantly lower in cut soleus and extensor digitorum longus muscles after incubation in vitro in contrast with respective control uncut muscles. These data indicate that cutting of muscle fibres alters rates of protein synthesis and degradation, in addition to altering concentrations of high-energy phosphates. Since these findings stressed the importance of using intact muscles to study protein metabolism, additional studies were made on intact muscles in vitro. Stretched soleus muscles had higher concentrations of high-energy phosphates at the end of an incubation period than did unstretched muscles. However, the length of the soleus, extensor digitorum longus and diaphragm muscles during incubation did not affect rates of protein degradation.

scholarly journals Effect of hypophysectomy on the rates of protein synthesis and degradation in rat liver

1979 ◽  
Vol 178 (3) ◽  
pp. 725-731 ◽  
Author(s):  
R D Conde
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Rat Liver ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Degradation Rates ◽  
Hypophysectomized Rats ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

The effect of hypophysectomy on the protein metabolism of the liver in vivo was studied. Fractional rates of protein synthesis and degradation were determined in the livers of normal and hypophysectomized rats. Synthesis was measured after the injection of massive amounts of radioactive leucine. Degradation was estimated either as the balance between synthesis and accumulation of stable liver proteins or from the disappearance of radioactivity from the proteins previously labelled by the injection of NaH14CO3. The results indicate that: (1) hypophysectomy diminishes the capacity of the liver to synthesize proteins in vivo, mainly of those that are exported as plasma proteins; (2) livers of both normal and hypophysectomized rats show identical protein-degradation rates, whereas plasma proteins are degraded slowly after hypophysectomy.

scholarly journals Specificity of the effects of leucine and its metabolites on protein degradation in skeletal muscle

1984 ◽  
Vol 222 (3) ◽  
pp. 579-586 ◽  
Author(s):  
W E Mitch ◽  
A S Clark
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Adult Rats ◽  
Limb Muscles ◽  
Leucine Catabolism ◽  
Muscle Protein Degradation ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

The effects of leucine, its metabolites, and the 2-oxo acids of valine and isoleucine on protein synthesis and degradation in incubated limb muscles of immature and adult rats were tested. Leucine stimulated protein synthesis but did not reduce proteolysis when leucine transamination was inhibited. 4-Methyl-2-oxopentanoate at concentrations as low as 0.25 mM inhibited protein degradation but did not change protein synthesis. The 2-oxo acids of valine and isoleucine did not change protein synthesis or degradation even at concentrations as high as 5 mM. 3-Methylvalerate, the irreversibly decarboxylated product of 4-methyl-2-oxopentanoate, decreased protein degradation at concentrations greater than or equal to 1 mM. This was not due to inhibition of 4-methyl-2-oxopentanoate catabolism, because 0.5 mM-3-methylvalerate did not suppress proteolysis, even though it inhibited leucine decarboxylation by 30%; higher concentrations of 3-methylvalerate decreased proteolysis progressively without inhibiting leucine decarboxylation further. During incubation with [1-14C]- and [U-14C]-leucine, it was found that products of leucine catabolism formed subsequent to the decarboxylation of 4-methyl-2-oxopentanoate accumulated intracellularly. This pattern was not seen during incubation with radiolabelled valine. Thus, the effect of leucine on muscle proteolysis requires transamination to 4-methyl-2-oxopentanoate. The inhibition of muscle protein degradation by leucine is most sensitive to, but not specific for, its 2-oxo acid, 4-methyl-2-oxopentanoate.

scholarly journals Regulation of protein synthesis and degradation in L8 myotubes. Effects of serum, insulin and insulin-like growth factors

1989 ◽  
Vol 260 (2) ◽  
pp. 377-387 ◽  
Author(s):  
E A Gulve ◽  
J F Dice
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Protein Degradation ◽  
Small Proportion ◽  
Serum Insulin ◽  
Horse Serum ◽  
Muscle Growth ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Insulin Like Growth Factors

We have examined the regulation of protein turnover in rat skeletal myotubes from the L8 cell line. We measured protein synthesis by the rates of incorporation of radiolabelled tyrosine into protein in the presence of a flooding dose of non-radioactive tyrosine. We monitored degradation of proteins labelled with radioactive tyrosine by the release of acid-soluble radioactivity into medium containing excess nonradioactive tyrosine. Extracellular tyrosine pools and intracellular tyrosyl-tRNA equilibrate rapidly during measurements of protein synthesis, and very little reutilization of the radiolabelled tyrosine occurs during degradation measurements. Measured rates of protein synthesis and degradation are constant for several hours, and changes in myotube protein content can be accurately predicted by the measured rates of protein synthesis and degradation. Most of the myotube proteins labelled with radioactive tyrosine for 2 days are degraded, with half-lives (t1/2) of approx. 50 h. A small proportion (less than 2.5%) of the radiolabelled proteins are degraded more rapidly (t1/2 less than 10 h), and, at most, a small proportion (less than 15%) are degraded more slowly (t1/2 greater than 50 h). A variety of agents commonly added to primary muscle cell cultures or to myoblast cell lines (18% Medium 199, 1% chick-embryo extract, antibiotics and antifungal agents) had no effect on rates of protein synthesis or degradation. Horse serum, fetal bovine serum and insulin stimulate protein synthesis and inhibit the degradation of long-lived proteins without affecting the degradation of short-lived proteins. Insulin-like growth factors (IGF)-1 and -2 also stimulate protein synthesis and inhibit protein degradation. The stimulation of protein synthesis and the inhibition of protein degradation are of similar magnitude (a maximum of approx. 2-fold) and display similar sensitivities to a particular anabolic agent. Insulin stimulates protein synthesis and inhibits protein degradation only at supraphysiological doses, whereas IGF-1 and -2 are effective at physiological concentrations. These and other findings suggest that IGFs may be important regulators of skeletal muscle growth during the fetal and early neonatal periods.

Protein synthesis and degradation in skeletal muscle of normal and dystrophic hamsters

1980 ◽  
Vol 239 (6) ◽  
pp. E401-E406
Author(s):  
J. B. Li
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Body Weights ◽  
Insulin Dependent ◽  
Muscle Protein Degradation ◽  
Lysosomal Proteases ◽  
Synthesis And Degradation

Dystrophic hamsters (BIO 53.58) had lower body weights and gastrocnemius muscle weights than normal hamsters (BIO RB). Dystrophic muscle contained less protein than normal muscle. The proportion of collagenous to noncollagenous protein remained unchanged. Loss of protein in the dystrophic muscle was the result of an increase in the rate of protein degradation. This was accompanied by higher activities of two lysosomal proteases, cathepsins B and D. The net effect of the increase in protein degradation was blunted by an increase in the rate of synthesis of total protein and myosin. The faster rate of synthesis in dystrophic muscle was partially due to an increase in the concentration of cellular RNA. Rates of peptide-chain initiation and protein synthesis decreased in muscles of normal hamsters perfused in the absence of insulin. In the presence of insulin, these processes were maintained at higher rates. However, the rate of protein synthesis in dystrophic muscle appeared less insulin-dependent than normal muscle. Protein degradation was inhibited by insulin in both types of muscle.

Effect of insulin on protein synthesis and degradation in skeletal muscle after exercise

1990 ◽  
Vol 258 (1) ◽  
pp. E92-E97 ◽  
Author(s):  
T. W. Balon ◽  
A. Zorzano ◽  
J. L. Treadway ◽  
M. N. Goodman ◽  
N. B. Ruderman
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Moderate Intensity ◽  
Control Group ◽  
Intense Exercise ◽  
Rat Muscle ◽  
The Difference ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Stimulation Of

This study examined whether insulin stimulation of protein synthesis and inhibition of protein degradation is enhanced after exercise. The isolated perfused rat hindquarter preparation was used to evaluate net protein breakdown, myofibrillar protein degradation, and protein synthesis. Thirty minutes after treadmill exercise of high and moderate intensity, rates of tyrosine release were increased by 58 and 25%, respectively. Insulin at 75 microU/ml had no effect on these increases after intense exercise; however, 20,000 microU/ml of insulin totally inhibited this increase. Cycloheximide increased the tyrosine release in both control and exercised rat muscle. It also abolished the difference between them, suggesting that the increase in tyrosine release after exercise is caused by an inhibition of protein synthesis. Phenylalanine incorporation into protein was marginally depressed (22%, P = NS) in the white gastrocnemius muscle after intense exercise. Insulin at 200 microU/ml stimulated protein synthesis in these rats, but no more than it did in a nonexercised control group. Failure to observe a greater effect of insulin on protein metabolism was also noted when rat muscle was studied 150 min after intense exercise and after contractions induced by electrical stimulation of the sciatic nerve. These findings suggest that after exercise or electrically induced contractions the enhanced ability of insulin to stimulate hexose and amino acid transport is not paralleled by an increase in its ability to stimulate protein synthesis or inhibit protein degradation.

scholarly journals Pentoxifylline improves insulin action limiting skeletal muscle catabolism after infection

1999 ◽  
Vol 163 (1) ◽  
pp. 15-24 ◽  
Author(s):  
T Vary ◽  
D Dardevet ◽  
J Grizard ◽  
L Voisin ◽  
C Buffiere ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

We investigated the ability of pentoxifylline (PTX) to modulate protein synthesis and degradation in the presence and absence of insulin during incubation of epitrochlearis muscle, 2 or 6 days after injection of Escherichia coli. On days 2 and 6 after infection, protein synthesis was inhibited by 25%, whereas proteolysis was enhanced by 75%. Insulin (2 nM) in vitro stimulated protein synthesis in muscles from infected rats to the same extent as in controls. The ability of insulin to limit protein degradation was severely blunted 48 h after infection. On day 6 after infection, insulin inhibited proteolysis to a greater extent than on day 2. PTX suppressed the increase in plasma concentrations of tumor necrosis factor more than 600-fold after injection of bacteria, and partially prevented the inhibition of protein synthesis and stimulation of protein degradation during sepsis. Moreover, PTX administration maintained the responsiveness of protein degradation to insulin during sepsis. Thus cytokines may influence skeletal muscle protein metabolism during sepsis, both indirectly through inhibition of the effects of insulin on proteolysis, and directly on the protein synthesis and degradation machinery.

scholarly journals Effects of dietary protein intake on muscle protein synthesis and degradation in rats with gentamicin-induced acute renal failure.

1991 ◽  
Vol 1 (11) ◽  
pp. 1230-1235
Author(s):  
R Baliga ◽  
S V Shah
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Isotonic Saline ◽  
Net Protein ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

In the study presented here, the muscle protein synthesis and degradation in gentamicin-induced acute renal failure were examined in rats fed a low (7%)-, normal (22%)-, and high (35%)-isocaloric protein diet. Male Sprague-Dawley rats were fed equivalent amounts of these diets for 10 days and then received daily subcutaneous injections of either 1 mL of sterile isotonic saline or 100 mg/kg of gentamicin for 7 consecutive days. The rats were sacrificed the following day, and epitrochlearis muscles were obtained for measurement of protein turnover. The serum creatinine in each of the gentamicin-treated groups were significantly higher than that in the saline-treated controls but were no different from each other. Muscle protein synthesis (calculated from the incorporation of radiolabeled (U-14C) phenylalanine) was slightly but not significantly decreased in gentamicin-treated rats as compared with that of the corresponding saline controls in each of the dietary groups. Net protein degradation (the rate of tyrosine release into media) in the 7 and 22% gentamicin-treated groups was similar to that in the corresponding saline controls. In contrast, net protein degradation was significantly greater in the 35% gentamicin group of rats when compared with that in the 7 and 22% gentamicin groups and its own control. In the 7 and 22% saline- and gentamicin-treated protein groups, there was a reduction in net protein degradation in response to insulin. In contrast, the net protein degradation continued to remain significantly elevated in the 35% gentamicin-treated group, despite addition of insulin, when compared with that in the 7 and 22% gentamicin groups and its own control.(ABSTRACT TRUNCATED AT 250 WORDS)

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