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

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.

Download Full-text

Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.1.173 ◽

1986 ◽

Vol 61 (1) ◽

pp. 173-179 ◽

Cited By ~ 81

Author(s):

P. Loughna ◽

G. Goldspink ◽

D. F. Goldspink

Keyword(s):

Soleus Muscle ◽

Muscle Length ◽

Protein Breakdown ◽

Fractional Rate ◽

Hindlimb Muscles ◽

Synthetic Rate ◽

Suspension Model ◽

Fast Twitch ◽

Passive Stretch

A state of hypokinesia and hypodynamia has been induced in the hindlimb muscles of the rat (100 g) using a suspension model. The ensuing muscle atrophy was assessed by reference to muscles in fully mobile control animals, which were either fed ad libitum or fed the same lower food intake of the suspended animals. Over a total of 7 days of suspension the slow-twitch postural soleus muscle underwent a much greater atrophy than the fast-twitch phasic extensor digitorum longus. Changes with respect to the position of the suspended foot, and hence muscle length, necessitate caution in comparing the extent of the atrophy between different muscle types. After 3 days of inactivity the atrophy of the soleus muscle was explained by a 21% decrease in the fractional rate of synthesis (measured in vivo) and a 100% increase in the rate of protein breakdown. The reduction in the synthetic rate was associated with a net loss (23%) of RNA and hence muscle ribosomes. In contrast when this inactive soleus muscle was permanently stretched the RNA content (44%) and protein synthetic rate increased (59%) markedly above control values. Although protein breakdown remained elevated in this stretched muscle, the extent of the atrophy in response to hypokinesia and hypodynamia was greatly reduced.

Download Full-text

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.6.e828 ◽

1989 ◽

Vol 257 (6) ◽

pp. E828-E832 ◽

Cited By ~ 12

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.

Download Full-text

The influence of passive stretch on the growth and protein turnover of the denervated extensor digitorum longus muscle

Biochemical Journal ◽

10.1042/bj1740595 ◽

1978 ◽

Vol 174 (2) ◽

pp. 595-602 ◽

Cited By ~ 66

Author(s):

David F. Goldspink

Keyword(s):

Protein Synthesis ◽

Extensor Digitorum Longus ◽

Similar Rate ◽

Extensor Digitorum Longus Muscle ◽

Extensor Digitorum ◽

Denervated Muscle ◽

Longus Muscle ◽

Induced Changes ◽

Passive Stretch

At 7 days after cutting the sciatic nerve, the extensor digitorum longus muscle was smaller and contained less protein than its innervated control. Correlating with these changes was the finding of elevated rates of protein degradation (measured in vitro) in the denervated tissue. However, at this time, rates of protein synthesis (measured in vitro) and nucleic acid concentrations were also higher in the denervated tissue, changes more usually associated with an active muscle rather than a disused one. These anabolic trends have, at least in part, been explained by the possible greater exposure of the denervated extensor digitorum longus to passive stretch. When immobilized under a maintained influence of stretch the denervated muscle grew to a greater extent. Although this stretch-induced growth appeared to occur predominantly through a stimulation of protein synthesis, it was opposed by smaller increases in degradative rates. Nucleic acids increased at a similar rate to the increase in muscle mass when a continuous influence of stretch was imposed on the denervated tissue. In contrast, immobilization of the denervated extensor digitorum longus in a shortened unstretched state reversed most of the stretch-induced changes; that is, the muscle became even smaller, with protein synthesis decreasing to a greater extent than breakdown after the removal of passive stretch. The present investigation suggests that stretch will promote protein synthesis and hence growth of the extensor digitorum longus even in the absence of an intact nerve supply. However, some factor(s), in addition to passive stretch, must contribute to the anabolic trends in this denervated muscle.

Download Full-text

Changes in protein turnover in rat uterus during pregnancy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.250.2.e114 ◽

1986 ◽

Vol 250 (2) ◽

pp. E114-E120 ◽

Cited By ~ 1

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.

Download Full-text

Chloroquine reduces whole body proteolysis in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.1.e183 ◽

1994 ◽

Vol 267 (1) ◽

pp. E183-E186 ◽

Cited By ~ 2

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.

Download Full-text

Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats

Biochemical Journal ◽

10.1042/bj2220395 ◽

1984 ◽

Vol 222 (2) ◽

pp. 395-400 ◽

Cited By ~ 34

Author(s):

V R Preedy ◽

D M Smith ◽

N F Kearney ◽

P H Sugden

Keyword(s):

Protein Synthesis ◽

Protein Degradation ◽

Protein Turnover ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Ventricular Muscle ◽

Degradation Rates ◽

Perfused Hearts

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

Download Full-text

A comparison of rates of protein turnover in rat diaphragm in vivo and in vitro

Biochemical Journal ◽

10.1042/bj2330279 ◽

1986 ◽

Vol 233 (1) ◽

pp. 279-282 ◽

Cited By ~ 11

Author(s):

V R Preedy ◽

D M Smith ◽

P H Sugden

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Rat Diaphragm ◽

Degradation Rates ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation

Protein synthesis and degradation rates in diaphragms from fed or starved rats were compared in vivo and in vitro. For fed rats, synthesis rates in vivo were approximately twice those in vitro, but for starved rats rates were similar. Degradation rates were less in vivo than in vitro in diaphragms from either fed or starved rats.

Download Full-text

Effect of parenteral nutrition on protein turnover in endotoxaemic rats

Clinical Science ◽

10.1042/cs0760659 ◽

1989 ◽

Vol 76 (6) ◽

pp. 659-666 ◽

Cited By ~ 22

Author(s):

S. A. Ash ◽

G. E. Griffin

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Protein Synthesis ◽

Food Intake ◽

Parenteral Nutrition ◽

Total Parenteral Nutrition ◽

Intravenous Infusion ◽

Protein Turnover

1. Intravenous infusion of endotoxin into rats over 18 h caused a reduction in food intake to 20% of normal levels, weight loss, hypoalbuminaemia and a fall in rates of protein synthesis in vivo in heart and skeletal muscle. 2. Measurements of protein turnover in vitro in skeletal muscle of endotoxaemic animals, showed a 50% fall in protein synthesis rates and a 200% increase in rates of protein degradation. 3. Total parenteral nutrition was only partially able to reverse endotoxin-induced weight loss. Total parenteral nutrition did not reverse endotoxin-induced catabolism in cardiac or skeletal muscle, but was able to reverse the catabolism of protein in skeletal muscle produced by starvation. 4. Endotoxin treatment elevated rates of protein synthesis in vivo in liver. The combination of parenteral nutrition and endotoxaemia further increased the rate of protein synthesis in the liver. Parenteral nutrition did not influence endotoxin-induced hypoalbuminaemia.

Download Full-text

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

Biochemical Journal ◽

10.1042/bj2060641 ◽

1982 ◽

Vol 206 (3) ◽

pp. 641-645 ◽

Cited By ~ 70

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.

Download Full-text