scholarly journals Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

2019 ◽  
Author(s):  
Xia Yan ◽  
Xuli Gao ◽  
Xin Peng ◽  
Jie Zhang ◽  
Xiufeng Ma ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Regeneration ◽  
Protein Metabolism ◽  
Muscle Hypertrophy ◽  
Gastrocnemius Muscle ◽  
Fiber Type ◽  
Ground Squirrels ◽  
Diaphragm Muscle ◽  
Gastrocnemius Muscles

AbstractWhether differences in regulation of protein metabolism and regeneration are involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA), fiber type distribution, and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1, and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1, and LC3-II), and muscle regeneration (MyoD, myogenin, and myostatin). Results showed the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4% in the hibernation group compared with the summer active group. Both muscles displayed a significant fast-to-slow fiber-type transition in hibernation. Our study further indicated that increased protein synthesis, decreased protein degradation, and increased muscle regeneration potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation, and decreased muscle regeneration potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism may contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.

scholarly journals Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver

1997 ◽  
Vol 77 (2) ◽  
pp. 197-212 ◽  
Author(s):  
Jens Kondrup ◽  
Klaus Nielsen ◽  
Anders Juul
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Cirrhosis Of The Liver ◽  
N Balance ◽  
Whole Body ◽  
Protein Requirement ◽  
Protein Utilization ◽  
Igf I

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.

scholarly journals Effects of intramuscular administration of 1α,25(OH)2D3 during skeletal muscle regeneration on regenerative capacity, muscular fibrosis, and angiogenesis

2016 ◽  
Vol 120 (12) ◽  
pp. 1381-1393 ◽  
Author(s):  
Ratchakrit Srikuea ◽  
Muthita Hirunsai
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Protein Synthesis ◽  
Cell Differentiation ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Fiber Type ◽  
Fiber Formation ◽  
Skeletal Muscle Regeneration ◽  
Type Composition

The recent discovery of the vitamin D receptor (VDR) in regenerating muscle raises the question regarding the action of vitamin D3 on skeletal muscle regeneration. To investigate the action of vitamin D3 on this process, the tibialis anterior muscle of male C57BL/6 mice (10 wk of age) was injected with 1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3 [1α,25(OH)2D3] was administered daily via intramuscular injections during the regenerative phase (days 4-7 postinjury). Physiological and supraphysiological doses of 1α,25(OH)2D3 relative to 1 μg/kg muscle wet weight and mouse body weight were investigated. Muscle samples were collected on day 8 postinjury to examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1), satellite cell differentiation and regenerative muscle fiber formation [myogenin and embryonic myosin heavy chain (EbMHC)], protein synthesis signaling (Akt, p70 S6K1, 4E-BP1, and myostatin), fiber-type composition (fast and slow MHCs), fibrous formation (vimentin), and angiogenesis (CD31). Administration of 1α,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was increased, accompanying decreased myogenin and EbMHC expression at the supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1, 4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose investigated. Taken together, administration of 1α,25(OH)2D3 at a supraphysiological dose decreased satellite cell differentiation, delayed regenerative muscle fiber formation, and increased muscular fibrosis. However, protein synthesis signaling, fiber-type composition, and angiogenesis were not affected by either 1α,25(OH)2D3 administration at a physiological or supraphysiological dose.

scholarly journals Effects of insulin in vitro on protein turnover in rat epitrochlearis muscle

1983 ◽  
Vol 210 (2) ◽  
pp. 323-330 ◽  
Author(s):  
W S Stirewalt ◽  
R B Low
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Nitrogen Balance ◽  
Protein Metabolism ◽  
Serum Insulin ◽  
Specific Radioactivity ◽  
Physiological Concentration ◽  
Rat Serum ◽  
The Third

Rates of protein synthesis and degradation were measured in the isolated rat epitrochlearis muscle by radiotracer techniques, by using the specific radioactivity of tRNA-bound amino acid as precursor for protein synthesis. The tissue maintained linear rates of protein synthesis for 3 h of incubation in the presence of amino acids and glucose and in the absence of insulin. Under these conditions, however, the muscles were in negative nitrogen balance, with rates of protein degradation exceeding rates of protein synthesis. Under steady-state conditions of labelling, the specific radioactivities of tRNA-bound leucine, phenylalanine and valine were significantly less than their respective values in the incubation medium, at concentrations in the medium varying from 1 to 10 times those in normal rat serum. Insulin caused a dose- and time-dependent increase in tRNA-based protein synthesis rates, more than doubling rates at 5 and 50 ng of insulin/ml. At the lower, physiological, concentration of insulin, the stimulation of protein synthesis was not observed until the third hour of incubation with the hormone, whereas the rate of protein synthesis at the higher concentration was elevated during the second hour. There were no delays in the stimulation by insulin of glucose conversion into glycogen. The delayed stimulatory effects of insulin on the rate of protein synthesis brought the tissue to a nitrogen balance near zero. The presence of the hormone also prevented the increase in the rate of protein degradation seen in the third hour of incubation in the absence of the hormone. These studies demonstrate the viability of the incubated rat epitrochlearis muscle with respect to protein metabolism and sensitivity to the protein anabolic effects of physiological concentrations of insulin, and indicate that the preparation is a suitable experimental model for the study of the control of protein metabolism in fast-twitch skeletal muscle.

scholarly journals The effect of denervation on protein synthesis and degradation in adult rat diaphragm muscle

2009 ◽  
Vol 107 (2) ◽  
pp. 438-444 ◽  
Author(s):  
Heather M. Argadine ◽  
Nathan J. Hellyer ◽  
Carlos B. Mantilla ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Caspase 3 ◽  
Diaphragm Muscle ◽  
Rat Diaphragm ◽  
Ubiquitin Proteasome Pathway ◽  
Protein Ubiquitination ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Net Protein

Previous studies showed that unilateral denervation (DNV) of the rat diaphragm muscle (DIAm) results in loss of myosin heavy chain protein by 1 day after DNV. We hypothesize that DNV decreases net protein balance as a result of activation of the ubiquitin-proteasome pathway. In DIAm strips, protein synthesis was measured by incorporation of 3H-Tyr, and protein degradation was measured by Tyr release at 1, 3, 5, 7, and 14 days after DNV. Total protein ubiquitination, caspase-3 expression/activity, and actin fragmentation were analyzed by Western analysis. We found that, at 3 days after DNV, protein synthesis increased by 77% relative to sham controls. Protein synthesis remained elevated at 5 (85%), 7 (53%), and 14 days (123%) after DNV. At 5 days after DNV, protein degradation increased by 43% relative to sham controls and remained elevated at 7 (49%) and 14 days (74%) after DNV. Thus, by 5 days after DNV, net protein balance decreased by 43% compared with sham controls and was decreased compared with sham at 7 (49%) and 14 days (72%) after DNV. Protein ubiquitination increased at 5 days after DNV and remained elevated. DNV had no effect on caspase-3 activity or actin fragmentation, suggesting that the ubiquitin-proteasome pathway rather than caspase-3 activation is important in the DIAm response to DNV. Early loss of contractile proteins, such as myosin heavy chain, is likely the result of selective protein degradation rather than generalized protein breakdown. Future studies should evaluate this selective effect of DNV.

scholarly journals Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats

2017 ◽  
Vol 122 (5) ◽  
pp. 1336-1350 ◽  
Author(s):  
Leslie M. Baehr ◽  
Daniel W. D. West ◽  
Andrea G. Marshall ◽  
George R. Marcotte ◽  
Keith Baar ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Hindlimb Unloading ◽  
Medial Gastrocnemius ◽  
Old Rats ◽  
The Impact

Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age, is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius, and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7, or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (−9 to −38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles, except for the old TA. Atrophy-associated gene expression was only loosely associated with protein degradation as muscle RING finger-1, muscle atrophy F-box (MAFbx), and Forkhead box O1 expression significantly increased in all muscles, but an increase in proteasome activity was only observed in the adult soleus. MAFbx protein levels were significantly higher in the old muscles compared with adult muscles, despite the old having higher expression of microRNA-23a. These results indicate that adult and old muscles respond similarly to HU, and the greatest loss in muscle mass occurs in predominantly slow-twitch extensor muscles due to a concomitant decrease in protein synthesis and increase in protein degradation. NEW & NOTEWORTHY In this study, we showed that age did not intensify the atrophy response to unloading in rats, but rather that the degree of atrophy was highly variable across muscles, indicating that changes in protein synthesis and protein degradation occur in a muscle-specific manner. Our data emphasize the importance of studying muscles of varying fiber-type and physiological function at multiple time points to fully understand the molecular mechanisms responsible for disuse atrophy.

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 Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia

1998 ◽  
Vol 275 (4) ◽  
pp. E584-E593 ◽  
Author(s):  
Thomas C. Vary ◽  
Dominique Dardevet ◽  
Jean Grizard ◽  
Laure Voisin ◽  
Caroline Buffiere ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Metabolic Response ◽  
Muscle Protein ◽  
Limited Proteolysis ◽  
Skeletal Muscle Protein ◽  
Protein Balance ◽  
Igf I

Skeletal muscle catabolism is a characteristic metabolic response to sepsis. We investigated the ability of physiological insulin (2 nM) or insulin-like growth factor I (IGF-I, 10 nM) concentrations to modify protein metabolism during incubation of epitrochlearis 2, 6, or 15 days after injection of live Escherichia coli. On days 2 and 6 postinfection, skeletal muscle exhibited an exacerbated negative protein balance resulting from both an inhibition in protein synthesis (25%) and an enhanced proteolysis (90%) compared with controls. By day 15 postinfection, protein balance in infected rats was significantly improved compared with either day 2 or 6. At this time, protein synthesis was augmented and protein degradation was decreased in infected rats relative to day 6. Insulin or IGF-I stimulated protein synthesis in muscles from septic and control rats in vitro to the same extent at each time point examined. The ability of insulin or IGF-I to limit protein degradation was severely blunted 48 h after infection. On day 6 postinfection, the effect of insulin or IGF-I to inhibit proteolysis was more pronounced than on day 2. Incubation with IGF-I limited proteolysis to a greater extent than insulin on both days in infected but not control rats. By day 15, insulin diminished proteolysis to the same extent as in controls. The results suggest that injection of bacteria causes fundamental derangements in protein metabolism that persist for days after infection.

scholarly journals Genetic Strain-Dependent Protein Metabolism and Muscle Hypertrophy Under Chronic Isometric Training in Rat Gastrocnemius Muscle

2012 ◽  
pp. 527-535 ◽  
Author(s):  
K. KOBAYASHI ◽  
R. OGASAWARA ◽  
A. TSUTAKI ◽  
K. LEE ◽  
E. OCHI ◽  
...  
Keyword(s):  
Protein Metabolism ◽  
Wistar Rats ◽  
Muscle Hypertrophy ◽  
Gastrocnemius Muscle ◽  
Strain Difference ◽  
Mechanical Stimuli ◽  
Sd Rats ◽  
Genetic Strain ◽  
Significant Difference ◽  
Strain Dependent

Genetic strain-dependent reactivity to mechanical stimuli in rat skeletal muscle has not been examined. This study aimed to examine whether genetic strain-dependency is associated with reactivity in protein metabolism and the resultant muscle hypertrophy after isometric resistance training (RT). The right triceps of Sprague-Dawley (SD) and Wistar rats underwent 12 sessions of RT. After RT, a transition from the IIb to the IIx myosin heavy-chain isoform was observed in both strains. In SD rats, the lateral gastrocnemius muscle (LG) mass of the trained legs (TRN) was significantly higher than that of the control legs (CON) (7.8 %, P<0.05). Meanwhile, in Wistar rats, the LG mass was unchanged. In SD rats, the levels of 70-kDa ribosomal protein S6 kinase (p70S6k) and forkhead box 3a (FOXO3a) phosphorylation in the TRN were significantly greater than those of the CON (2.2- and 1.9-fold, respectively; P<0.05). The expression of muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) in the TRN were significantly lower than those of the CON (0.6- and 0.7-fold, respectively; P<0.05). However, in Wistar rats, there was no significant difference. These results suggest a genetic strain difference in protein metabolism. This phenomenon may be useful for studying individual differences in response to RT.

Somatotropin-induced protein anabolism in hindquarters and portal-drained viscera of growing pigs

2003 ◽  
Vol 284 (2) ◽  
pp. E302-E312 ◽  
Author(s):  
Jill A. Bush ◽  
Douglas G. Burrin ◽  
Agus Suryawan ◽  
Pamela M. J. O'Connor ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Growing Pigs ◽  
Whole Body ◽  
Fed State

To differentiate the effect of somatotropin (ST) treatment on protein metabolism in the hindquarter (HQ) and portal-drained viscera (PDV), growing swine ( n = 20) treated with ST (0 or 150 μg · kg−1 · day−1) for 7 days were infused intravenously with NaH13CO3 and [2H5]phenylalanine and enterally with [1-13C]phenylalanine while in the fed state. Arterial, portal venous, and vena cava whole blood samples, breath samples, and blood flow measurements were obtained for determination of tissue and whole body phenylalanine kinetics under steady-state conditions. In the fed state, ST treatment decreased whole body phenylalanine flux, oxidation, and protein degradation without altering protein synthesis, resulting in an improvement in whole body net protein balance. Blood flow to the HQ (+80%), but not to the PDV, was increased with ST treatment. In the HQ and PDV, ST increased phenylalanine uptake (+44 and +23%, respectively) and protein synthesis (+43 and +41%, respectively), with no effect on protein degradation. In ST-treated and control pigs, phenylalanine was oxidized in the PDV (34–43% of enteral and arterial sources) but not the HQ. In both treatment groups, dietary (40%) rather than arterial (10%) extraction of phenylalanine predominated in gut amino acid metabolism, whereas localized blood flow influenced HQ amino acid metabolism. The results indicate that ST increases protein anabolism in young, growing swine by increasing protein synthesis in the HQ and PDV, with no effect on protein degradation. Differing results between the whole body and the HQ and PDV suggest that the effect of ST treatment on protein metabolism is tissue specific.

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