scholarly journals Glucocorticoid action on protein synthesis and protein breakdown in isolated skeletal muscles

1982 ◽  
Vol 206 (3) ◽  
pp. 641-645 ◽  
Author(s):  
Josephine A. McGrath ◽  
David F. Goldspink
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Skeletal Muscles ◽  
Glucocorticoid Hormones ◽  
Protein Breakdown ◽  
Synthetic Steroids ◽  
Glucocorticoid Action

The direct actions of glucocorticoid hormones on protein turnover were studied in isolated soleus muscles. These steroids were found to decrease the rates of both protein synthesis and protein breakdown within 3 h and 4 h respectively. Synthetic steroids (e.g. dexamethasone) were found to be more potent than naturally secreted hormones (e.g. cortisol) in inducing these changes, but only at concentrations in vitro less than 10nm.

scholarly journals The effects of calcium on protein turnover in skeletal muscles of the rat

1982 ◽  
Vol 204 (1) ◽  
pp. 257-264 ◽  
Author(s):  
S E M Lewis ◽  
P Anderson ◽  
D F Goldspink
Keyword(s):  
Protein Synthesis ◽  
Cyclic Nucleotides ◽  
Protein Turnover ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Muscle Protein ◽  
Ionophore A23187 ◽  
Protein Breakdown ◽  
External Concentration ◽  
The Media

Several experimental procedures were used to increase the intracellular concentration of Ca2+ and determine its effects on protein turnover in isolated extensor digitorum longus and soleus muscle. These methods included the use of ionophore A23187, caffeine, dibucaine, thymol and procaine, all agents known to induce the release of calcium by acting either on the sarcolemma and/or on the sarcoplasmic reticulum. Another approach involved varying the external concentration of Ca2+ in the media in which the muscles were incubated. The changes in muscle Ca2+ concentrations after exposure to the various calcium-releasing agents were in keeping with accepted modes of action of these agents on muscle membranes. The findings suggest that increasing the sarcoplasmic concentration of Ca2+ inhibits protein synthesis and enhances protein breakdown. These catabolic effects of Ca2+ are compared with the changes induced in muscle protein turnover after exposure to insulin or cyclic nucleotides, and in myopathic muscle and situations of work overload. Attention is also drawn to some of the difficulties involved in definitively implicating Ca2+ as a factor involved in the normal regulation of protein turnover.

scholarly journals Protein turnover measured in vivo and in vitro in muscles undergoing compensatory growth and subsequent denervation atrophy

1983 ◽  
Vol 210 (1) ◽  
pp. 89-98 ◽  
Author(s):  
D F Goldspink ◽  
P J Garlick ◽  
M A McNurlan
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Compensatory Growth ◽  
Protein Breakdown ◽  
Synthetic Rate ◽  
Longus Muscle ◽  
Passive Stretch ◽  
Good Agreement

The rapid growth (1-6 days) of the functionally overloaded soleus muscle, in response to tenotomy of the synergist gastrocnemius, was found to correlate with increases in both the protein synthetic and degradative rates, the change in the former being greater than that of the latter. These conclusions were drawn from two different methods used to measure (in vivo and in vitro) the average rates of protein synthesis and protein breakdown in these soleus muscles. Although the basal rates of synthesis were higher when measured in vivo, and the degradative rates higher in isolated muscle preparations incubated in vitro, both methods gave good agreement concerning the changes in protein turnover induced by tenotomy of the gastrocnemius. The possible involvement of passive stretch in inducing this additional growth is discussed. As an antagonist to the soleus, growth of the extensor digitorum longus muscle was decreased under the same conditions, presumably because of less usage. At 3 days after the cutting of the sciatic nerve, the previously normal or overloaded soleus muscles underwent rapid atrophy. Although in both cases RNA and protein were lost, while protein synthesis decreased and protein breakdown increased, denervation induced larger changes within these parameters of the formerly overloaded muscle. The slowing of growth in the tenotomized gastrocnemius, and its subsequent rapid atrophy after additional denervation, were explained by large increases in protein breakdown, with little or no change in the synthetic rate.

Fiber-type composition of nine rat muscles. II. Relationship to protein turnover

1989 ◽  
Vol 257 (6) ◽  
pp. E828-E832 ◽  
Author(s):  
P. J. Garlick ◽  
C. A. Maltin ◽  
A. G. Baillie ◽  
M. I. Delday ◽  
D. A. Grubb
Keyword(s):  
Protein Synthesis ◽  
Regression Analysis ◽  
Protein Turnover ◽  
Fiber Type ◽  
Female Rats ◽  
Protein Breakdown ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Age Regression

Rates of protein synthesis in vivo and fiber-type composition were measured in nine limb muscles of female rats at ages ranging from weaning to 1 yr. In all muscles, there was a decline in protein synthesis with increasing age, mostly as a result of a fall in the RNA content. Rates of protein breakdown and growth were determined in six muscles and these also declined with age. Regression analysis of the data for all ages showed that protein synthesis was correlated with the content of slow oxidative fibers but not with the relative proportions of fast glycolytic to fast oxidative glycolytic fibers.

Effect of glutamine on leucine metabolism in humans

1996 ◽  
Vol 271 (4) ◽  
pp. E748-E754 ◽  
Author(s):  
R. G. Hankard ◽  
M. W. Haymond ◽  
D. Darmaun
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Specific Activity ◽  
Excretion Rate ◽  
The Other ◽  
Anabolic Effect ◽  
Protein Breakdown ◽  
Glutamine Concentration ◽  
Putative Protein

The aim of this study was to determine whether the putative protein anabolic effect of glutamine 1) is mediated by increased protein synthesis or decreased protein breakdown and 2) is specific to glutamine. Seven healthy adults were administered 5-h intravenous infusions of L-[1-14C]leucine in the postabsorptive state while receiving in a randomized order an enteral infusion of saline on one day or L-glutamine (800 mumol.kg-1.h-1, equivalent to 0.11 g N/kg) on the other day. Seven additional subjects were studied using the same protocol except they received isonitrogenous infusion of glycine. The rates of leucine appearance (RaLeu), an index of protein degradation, leucine oxidation (OxLeu), and nonoxidative leucine disposal (NOLD), an index of protein synthesis, were measured using the 14C specific activity of plasma alpha-ketoisocaproate and the excretion rate of 14CO2 in breath. During glutamine infusion, plasma glutamine concentration doubled (673 +/- 66 vs. 1,184 +/- 37 microM, P < 0.05), whereas RaLeu did not change (122 +/- 9 vs. 122 +/- 7 mumol. kg-1.h-1), OxLeu decreased (19 +/- 2 vs. 11 +/- 1 mumol.kg-1.h-1, P < 0.01), and NOLD increased (103 +/- 8 vs. 111 +/- 6 mumol. kg-1.h-1, P < 0.01). During glycine infusion, plasma glycine increased 14-fold (268 +/- 62 vs. 3,806 +/- 546 microM, P < 0.01), but, in contrast to glutamine, RaLeu (124 +/- 6 vs. 110 +/- 4 mumol. kg-1.h-1, P = 0.02), OxLeu (17 +/- 1 vs. 14 +/- 1 mumol.kg-1.h-1, P = 0.03), and NOLD (106 +/- 5 vs. 96 +/- 3 mumol.kg-1.h-1, P < 0.05) all decreased. We conclude that glutamine enteral infusion may exert its protein anabolic effect by increasing protein synthesis, whereas an isonitrogenous amount of glycine merely decreases protein turnover with only a small anabolic effect resulting from a greater decrease in proteolysis than protein synthesis.

Changes in protein turnover in rat uterus during pregnancy

1986 ◽  
Vol 250 (2) ◽  
pp. E114-E120 ◽  
Author(s):  
A. J. Morton ◽  
D. F. Goldspink
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Cathepsin D ◽  
Cell Loss ◽  
Protein Breakdown ◽  
Rat Uterus ◽  
Fractional Rate ◽  
Uterine Growth

The adaptive growth and protein turnover of the rat uterus were studied during the 21 days of gestation and up to 3 days after parturition. Despite large increases (13-fold) in uterine size during gestation, the fractional rate of protein synthesis (measured in vivo) remained unchanged when compared with nonpregnant tissue values of 44 +/- 5%/day. However, decreases were found in the rate of protein breakdown after implantation (i.e., 75% on day 7 and 28% on day 11) and in the activity of cathepsin D (i.e., 33 and 85% on days 8 and 16 of gestation). Changes in the degradative processes would therefore appear to be primarily responsible for the massive uterine growth during pregnancy. In contrast to the uterus the fractional rates of synthesis in the placenta and fetus progressively decreased during gestation. After parturition the uterus rapidly returned to its normal size by a combination of cellular atrophy and cell loss. After 2 days, a complementary decrease in the fractional rate of synthesis (30%) and an increase in protein degradation (2-fold) explained the process of involution.

Protein turnover in gravid and nongravid horns of uterus in pregnant rats

1988 ◽  
Vol 254 (5) ◽  
pp. E549-E554 ◽  
Author(s):  
D. F. Goldspink ◽  
A. J. Douglas
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Hormonal Changes ◽  
Protein Breakdown ◽  
Pregnant Rats ◽  
Fourfold Increase ◽  
Dna Contents ◽  
Extensive Growth ◽  
Rna And Dna ◽  
Marked Suppression

Changes in uterine protein, RNA, and DNA contents in gravid and nongravid horns from the same animal were studied after 14 and 16 days of pregnancy. At 16 days, all of these parameters of growth had increased between three- and sevenfold in the gravid horn while remaining unchanged in the nongravid horn compared with the uterus of nonpregnant control animals. In the nongravid horn, the hormonal changes associated with pregnancy induced antagonistic decreases in both the average rates of protein synthesis and protein breakdown, with the net result being no change in its growth. In the gravid horn, however, the hormonal influences are coupled with the stretching effects produced by the enlarging fetuses. Here the net effect was a marked suppression of protein breakdown, resulting in a fourfold increase in its rate of growth. These data, together with those derived from analysis of both fetal and nonfetal sites from the gravid horn, led to the following conclusions. Changes in circulating hormones during pregnancy do not alone appear to influence the overall size of the uterus. In contrast, mechanical distension of the uterus promotes rapid and extensive growth.

Chloroquine reduces whole body proteolysis in humans

1994 ◽  
Vol 267 (1) ◽  
pp. E183-E186 ◽  
Author(s):  
P. De Feo ◽  
E. Volpi ◽  
P. Lucidi ◽  
G. Cruciani ◽  
F. Santeusanio ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Lysosomal Proteolysis ◽  
Therapeutic Doses

The antimalaric drug chloroquine is a well known inhibitor of lysosomal proteolysis in vitro. The present study tests the hypothesis that therapeutic doses of the drug decrease proteolysis also in vivo in humans. Leucine kinetics were determined in 20 healthy volunteers given 12 and 1.5 h before the studies 250 and 500 mg, respectively, of chloroquine phosphate (n = 10) or similar tablets of placebo (n = 10). Chloroquine reduced the rates of leucine appearance, a measure of whole body proteolysis, from 2.45 +/- 0.08 to 2.19 +/- 0.08 mumol.kg-1.min-1 (P = 0.038) and those of nonoxidative leucine disposal, an estimate of whole body protein synthesis, from 2.16 +/- 0.08 to 1.95 +/- 0.06 mumol.kg-1.min-1 (P = 0.050). The drug resulted also in a marginally significant (P = 0.051) decrement in the plasma concentrations of glucose. The effects of chloroquine on protein turnover might be potentially useful in counteracting protein wasting complicating several catabolic diseases, whereas those on glucose metabolism can explain the sporadic occurrence of severe hypoglycemic episodes in malaria patients chronically treated with this drug.

Measurement of muscle protein degradation in live mice by accumulation of bestatin-induced peptides

1997 ◽  
Vol 273 (6) ◽  
pp. E1149-E1157 ◽  
Author(s):  
Violeta Botbol ◽  
Oscar A. Scornik
Keyword(s):  
Protein Degradation ◽  
Protein Turnover ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Cellular Proteins ◽  
Protein Breakdown ◽  
Maximum Accumulation ◽  
Muscle Protein Breakdown ◽  
Muscle Protein Degradation ◽  
Acute Changes

Bestatin, an aminopeptidase inhibitor, permits the degradation of cellular proteins to di- and tripeptides but interferes with the further breakdown of these peptides to amino acids. We propose to measure instant rates of protein degradation in skeletal muscles of intact mice by the accumulation of bestatin-induced intermediates. Muscle protein was labeled by injection ofl-[guanidino-14C]arginine; 3 days later, maximum accumulation of intermediates was measured in abdominal wall muscles 10 min after the intravenous injection of 5 mg of bestatin. The peptides were partially purified and hydrolyzed in 6 N HCl, and the radioactivity in peptide-derived arginine was determined, after conversion to14CO2by treatment with arginase and urease. The measurement of bestatin-induced intermediates provides a unique tool for studying acute changes in muscle protein turnover in live mice. We observed a 62% increase in muscle protein breakdown after a 16-h fast, which was reversed by refeeding for 3.5 h, and a 38% increase after 3 days of protein depletion.

scholarly journals The effects of 6 hours of hypoxia on protein synthesis in rat tissues in vivo and in vitro

1985 ◽  
Vol 228 (1) ◽  
pp. 179-185 ◽  
Author(s):  
V R Preedy ◽  
D M Smith ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Gastric Emptying ◽  
Skeletal Muscles ◽  
Rat Tissues ◽  
Tissue Nitrogen ◽  
The Brain ◽  
H Protein

Rates of protein synthesis were measured in vivo in several tissues (heart, skeletal muscles, liver, tibia, skin, brain, kidney, lung) of fed rats exposed to O2/N2 (1:9) for 6 h starting at 08:00-11:00 h. Protein synthesis rates were depressed by 15-35% compared with normoxic controls in all of the tissues studied. The decreases were greatest in the brain and the skin. Although hypoxia inhibited gastric emptying, its effects on protein synthesis could probably not be attributed to its induction of a starved state, because protein-synthesis rates in brain and skin were not decreased by a 15-18 h period of starvation initiated at 23:00 h. Furthermore, we showed that protein synthesis was inhibited by hypoxia in the rat heart perfused in vitro, suggesting a direct effect. The role of hypoxia in perturbing tissue nitrogen balance in various physiological and pathological states is discussed.

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