The effect of surgical trauma on muscle protein turnover in rats. A serious methodological misunderstanding.
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ABSTRACT:
SUBMITTER: Millward DJ
PROVIDER: S-EPMC1161068 | biostudies-other | 1979 May
REPOSITORIES: biostudies-other
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Project description:The rate of synthesis and catabolism of sarcoplasmic- and myofibrillar-muscle protein was measured in operated, sham-operated and food-restricted rats by using Na2 14CO3. The food-restricted group underwent sham operations and were limited to the food intake of the operated animals. Protein synthesis and catabolism were increased in the sarcoplasmic-muscle fraction in operated rats compared with that in sham-operated or food-restricted rats. The rate of synthesis of the myofibrillar protein decreased in operated animals, but the rate of catabolism was not altered in the myofibrillar-muscle fraction of the operated animals compared with that in food-restricted and sham-operated animals. In the operated animals, there was a net loss of protein from the muscle. Thus the rats that underwent surgery lost muscle protein, primarily as a result of a decrease in synthesis of myofibrillar protein. The changes in protein turnover in operated animals were not due to decreases in food intake, since protein turnover in sham-operated animals that were restricted to the food intake of the operated rats was not different from that in sham-operated rats fed ad libitum.
| S-EPMC1186213 | biostudies-other
Project description:BACKGROUND & AIMS:Burns remain the fifth cause of non-fatal pediatric injuries globally, with muscle cachexia being a hallmark of the stress response to burns. Burn-induced muscle wasting is associated with morbidity, yet the determinants of muscle protein catabolism in response to burn trauma remains unclear. Our objective was to determine the effect of patient and injury characteristics on muscle protein kinetics in burn patients. METHODS:This retrospective, observational study was performed using protein kinetic data from pediatric patients who had severe burns (>30% of the total body surface area burned) and underwent cross-limb stable isotope infusions between 1999 and 2008 as part of prospective clinical trials. Mixed multiple regression models were used to assess associations between patient/injury characteristics and muscle protein fractional synthesis rate (FSR), net balance (NB), and rates of phenylalanine appearance (Ra; index of protein breakdown) and disappearance (Rd; index of protein synthesis) across the leg. RESULTS:A total of 268 patients who underwent 499 studies were analyzed. Increasing time post injury was associated with greater FSR (p < 0.001) and NB (p = 0.01). Males were more catabolic than females (as indicated by lower NB, p = 0.04 and greater Ra, p = 0.008), a consequence of higher protein breakdown rather than lower synthesis. Increasing burn size was associated with higher protein synthesis rate (as indicated by higher FSR, p = 0.019) and higher protein breakdown rates (as indicated by greater Ra, p = 0.001). FSR was negatively associated with age (p < 0.001). CONCLUSIONS:Data from this large patient cohort show that injury severity, sex, and time post injury influence skeletal muscle wasting in burned children. These findings suggest that individual patient characteristics should be considered when devising therapies to improve the acute care and rehabilitation of burn survivors.
| S-EPMC6279601 | biostudies-literature
Project description:The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [(14)C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.
| S-EPMC1158405 | biostudies-other
Project description:Although protein turnover in skeletal muscle is increased in hyperthyroidism and decreased in hypothyroidism, a deficient protein intake tends to increase serum T3 (tri-iodothyronine) while decreasing muscle protein turnover. To determine whether this diet-induced decrease in protein turnover can occur independent of thyroid status, we have examined muscle protein turnover and nitrogen conservation in hyperthyroid rats fed on a protein-free diet. After inducing hyperthyroidism by giving 20 micrograms of T3/100g body wt. daily for 7 days, groups of euthyroid and hyperthyroid animals were divided into subgroups fed on basal and protein-free diets. Muscle protein turnover was measured by N tau-methylhistidine excretion and [14C]tyrosine infusion. Urinary nitrogen output of euthyroid and hyperthyroid animals fed on the protein-free diet was also measured. Although hyperthyroidism increased the baseline rates of muscle protein synthesis and degradation, it did not prevent a decrease in these values in response to protein depletion. Furthermore, hyperthyroid rats showed greatly decreased nitrogen excretion in response to the protein-free diet, although not to values for euthyroid rats. These findings suggest that protein depletion made the experimental animals less responsive to the protein-catabolic effects of T3.
| S-EPMC1153238 | biostudies-other
Project description:We have investigated the effects of thyroidectomy, hypophysectomy and 3,3',5-tri-iodothyronine replacement on protein synthesis and degradation in skeletal muscle in vivo. Thyroidectomy resulted in a decrease in the rate of protein synthesis as a result of a loss of RNA. However, RNA activity, the rate of protein synthesis per unit of RNA, was not decreased. This was the case in both young growing rats and mature nongrowing rats. Tri-iodothyronine treatment of thyroidectomized rats increased protein synthesis by increasing RNA concentration without changes in RNA activity, and this occurred even when food intake was restricted to prevent any increase in growth. The rate of protein degradation was decreased by thyroidectomy and increased by tri-iodo-thyronine replacement in both animals fed ad libitum and food-restricted animals. Hypophysectomy decreased protein synthesis by decreasing both RNA concentration and activity. these changes were reversed by tri-iodothyronine treatment even in the presence of persistent marked hypoinsulinaemia. This indicates that tri-iodothyronine can activate athe translational phase of protein synthesis in muscle in the absence of significant quantities of insulin. However, tri-iodothyronine does not seem to be obligatory for the maintenance of normal RNA activity in muscle, since in the thyroidectomized rat, in which plasma insulin concentrations are normal, RNA activity is maintained. From a consideration of the magnitude of changes in RNA activity observed in these experiments, it would appear that alterations in rates of elongation as well as initiation are involved in the changes in RNA activity.
| S-EPMC1162812 | biostudies-other
Project description:AimInterventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found that massage as a mechanotherapy can improve muscle regrowth following disuse atrophy. Therefore, we aimed to determine if massage has similar anabolic effects when applied during normal weight bearing conditions (WB) or during atrophy induced by hindlimb suspension (HS) in adult rats.MethodsAdult (10 months) male Fischer344-Brown Norway rats underwent either hindlimb suspension (HS, n = 8) or normal WB (WB, n = 8) for 7 days. Massage was applied using cyclic compressive loading (CCL) in WB (WBM, n = 9) or HS rats (HSM, n = 9) and included four 30-minute bouts of CCL applied to gastrocnemius muscle every other day.ResultsMassage had no effect on any anabolic parameter measured under WB conditions (WBM). In contrast, massage during HS (HSM) stimulated protein turnover, but did not mitigate muscle atrophy. Atrophy from HS was caused by both lowered protein synthesis and higher degradation. HS and HSM had lowered total RNA compared with WB and this was the result of significantly higher ribosome degradation in HS that was attenuated in HSM, without differences in ribosomal biogenesis. Also, massage increased protein turnover in the non-massaged contralateral limb during HS. Finally, we determined that total RNA degradation primarily dictates loss of muscle ribosomal content during disuse atrophy.ConclusionWe conclude that massage is an effective mechanotherapy to impact protein turnover during muscle disuse in both the massaged and non-massaged contralateral muscle, but it does not attenuate the loss of muscle mass.
| S-EPMC7293583 | biostudies-literature
Project description:Diffuse axonal injury (DAI) is a prevalent and serious brain injury with significant morbidity and disability. However, the underlying pathogenesis of DAI remains largely unclear, and there are still no objective laboratory-based tests available for clinicians to make an early diagnosis of DAI. An integrated analysis of metabolomic data and proteomic data may be useful to identify all of the molecular mechanisms of DAI and novel potential biomarkers. Therefore, we established a rat model of DAI, and applied an integrated UPLC-Q-TOF/MS-based metabolomics and isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to obtain unbiased profiling data. Differential analysis identified 34 metabolites and 43 proteins in rat plasma of the injury group. Two metabolites (acetone and 4-Hydroxybenzaldehyde) and two proteins (Alpha-1-antiproteinase and Alpha-1-acid glycoprotein) were identified as potential biomarkers for DAI, and all may play important roles in the pathogenesis of DAI. Our study demonstrated the feasibility of integrated metabolomics and proteomics method to uncover the underlying molecular mechanisms of DAI, and may help provide clinicians with some novel diagnostic biomarkers and therapeutic targets.
| S-EPMC6412711 | biostudies-literature
Project description:Rates of growth and protein turnover in the breast muscle of young chicks were measured in order to assess the roles of protein synthesis and degradation in the regulation of muscle mass. Rates of protein synthesis were measured in vivo by injecting a massive dose of L-[1-14C]valine, and rates of protein degradation were estimated as the difference between the synthesis rate and the growth rate of muscle protein. In chicks fed on a control diet for up to 7 weeks of age, the fractional rate of synthesis decreased from 1 to 2 weeks of age and then changed insignificantly from 2 to 7 weeks of age, whereas DNA activity was constant for 1 to 7 weeks. When 4-week-old chicks were fed on a protein-free diet for 17 days, the total amount of breast-muscle protein synthesized and degraded per day and the amount of protein synthesized per unit of DNA decreased. Protein was lost owing to a greater decrease in the rate of protein synthesis, as a result of the loss of RNA and a lowered RNA activity. When depleted chicks were re-fed the control diet, rapid growth was achieved by a doubling of the fractional synthesis rate by 2 days. Initially, this was a result of increased RNA activity; by 5 days, the RNA/DNA ratio also increased. There was no evidence of a decrease in the fractional degradation rate during re-feeding. These results indicate that dietary-protein depletion and repletion cause changes in breast-muscle protein mass primarily through changes in the rate of protein synthesis.
| S-EPMC1162817 | biostudies-other
Project description:Skeletal muscle atrophy is associated with a disruption in protein turnover involving increased protein degradation and suppressed protein synthesis. Although it has been well studied that the IGF-1/PI3K/Akt pathway plays an essential role in the regulation of the protein turnover, molecule(s) that triggers the change in protein turnover still remains to be elucidated. TRB3 has been shown to inhibit Akt through direct binding. In this study, we hypothesized that TRB3 in mouse skeletal muscle negatively regulates protein turnover via the disruption of Akt and its downstream molecules. Muscle-specific TRB3 transgenic (TRB3TG) mice had decreased muscle mass and fiber size, resulting in impaired muscle function. We also found that protein synthesis rate and signaling molecules, mTOR and S6K1, were significantly reduced in TRB3TG mice, whereas the protein breakdown pathway was significantly activated. In contrast, TRB3 knockout mice showed increased muscle mass and had an increase in protein synthesis rate, but decreases in FoxOs, atrogin-1, and MuRF-1. These findings indicate that TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways.
| S-EPMC5675010 | biostudies-literature
Project description:PurposeAcute bouts of resistance exercise and subsequent training alters protein turnover in skeletal muscle. The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown. Our goal was to determine whether post-absorptive muscle protein turnover following 12 weeks of resistance exercise training (RET) plays a role in muscle hypertrophy. In addition, we were interested in determining potential molecular mechanisms responsible for altering post-training muscle protein turnover.MethodsHealthy young men (n = 31) participated in supervised whole body progressive RET at 60-80% 1 repetition maximum (1-RM), 3 days/week for 3 months. Pre- and post-training vastus lateralis muscle biopsies and blood samples taken during an infusion of 13C6 and 15N phenylalanine and were used to assess skeletal muscle protein turnover in the post-absorptive state. Lean body mass (LBM), muscle strength (determined by dynamometry), vastus lateralis muscle thickness (MT), myofiber type-specific cross-sectional area (CSA), and mRNA were assessed pre- and post-RET.ResultsRET increased strength (12-40%), LBM (~5%), MT (~15%) and myofiber CSA (~20%) (p < 0.05). Muscle protein synthesis (MPS) increased 24% while muscle protein breakdown (MPB) decreased 21%, respectively. These changes in protein turnover resulted in an improved net muscle protein balance in the basal state following RET. Further, the change in basal MPS is positively associated (r = 0.555, p = 0.003) with the change in muscle thickness.ConclusionPost-absorptive muscle protein turnover is associated with muscle hypertrophy during resistance exercise training.
| S-EPMC5389914 | biostudies-literature