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muscle protein breakdown

Lorenza Brocca, Luana Toniolo, Carlo Reggiani, Roberto Bottinelli, Marco Sandri, Maria Antonietta Pellegrino
Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy program in the different disuse/inactivity conditions have not yet been completely dissected. It has been recently reported that inhibition of FoxO only partially spared muscle mass after denervation. The purposes of this study were: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model, (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation...
October 21, 2016: Journal of Physiology
Leandro H Manfredi, D Lustrino, Juliano Machado, Wilian Assis Silveira, Neusa Maria Zanon, Luiz C Navegantes, Isis do Carmo Kettelhut
Previous studies have shown that catecholamines in vivo and in vitro inhibit the activity of Ca(2+)-dependent proteolysis in skeletal muscles under basal conditions. In the present study we sought to investigate the role of catecholamines in regulating the Ca(2+)-dependent proteolysis in soleus and extensor digitorum longus (EDL) muscles from rats acutely exposed to cold. Overall proteolysis, the activity of proteolytic systems as well as protein levels and gene expression of different components of calpain system were investigated in rats submitted to adrenodemedullation (ADMX) and exposed to cold for 24 h...
October 20, 2016: Journal of Applied Physiology
Tadashi Yoshida, Patrice Delafontaine
Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II, via its type 1 receptor (AT1R), causes muscle protein breakdown and apoptosis, and inhibits satellite cell (SC) proliferation and muscle regeneration, likely contributing to cachexia in CHF and CKD. In contrast, AT2R expression is robustly induced during SC differentiation and it potentiates muscle regeneration. To understand mechanisms regulating AT2R expression and its potential role in muscle regeneration in chronic diseases we used a mouse model of CHF and found that muscle regeneration was markedly reduced and that this was accompanied by blunted increase of AT2R expression...
October 18, 2016: Journal of Biological Chemistry
Kristen T Crowell, David I Soybel, Charles H Lang
Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced...
October 5, 2016: Shock
Karen Vignale, Justina V Caldas, Judy A England, Nirun Boonsinchai, Phiphob Sodsee, Monticha Putsakum, Erik D Pollock, Sami Dridi, Craig N Coon
A study was conducted to evaluate the effect of four different feeding regimens on breast muscle protein turnover in broiler breeder Cobb-500 parent stock (PS) pullets and breeder hens. The four feeding regimens based on BW curves utilized for the study were as follows: Everyday feeding (STD-ED) (Cobb Standard BW curve), skip-a-day feeding (STD-SKIP) (Cobb Standard BW curve), lighter BW (LBW-SKIP) (BW curve 20% under), and heavier BW (HBW-SKIP) (BW curve 20% over). Each feeding regimen was provided to pullets from 4 wk to 21 wk of age...
October 12, 2016: Poultry Science
Annalisa Bonifacio, Gerda M Sanvee, Karin Brecht, Denise V Kratschmar, Alex Odermatt, Jamal Bouitbir, Stephan Krähenbühl
Statins are generally well tolerated, but treatment with these drugs may be associated with myopathy. The mechanisms of statin-associated myopathy are not completely understood. Statins inhibit AKT phosphorylation by an unclear mechanism, whereas insulin-like growth factor (IGF-1) activates the IGF-1/AKT signaling pathway and promotes muscle growth. The aims of the study were to investigate mechanisms of impaired AKT phosphorylation by simvastatin and to assess effects of IGF-1 on simvastatin-induced myotoxicity in C2C12 myotubes...
October 12, 2016: Archives of Toxicology
Stuart M Phillips
Protein supplementation during resistance exercise training augments hypertrophic gains. Protein ingestion and the resultant hyperaminoacidemia provides the building blocks (indispensable amino acids - IAA) for, and also triggers an increase in, muscle protein synthesis (MPS), suppression of muscle protein breakdown (MPB), and net positive protein balance (i.e., MPS > MPB). The key amino acid triggering the rise in MPS is leucine, which stimulates the mechanistic target of rapamycin complex-1, a key signalling protein, and triggers a rise in MPS...
2016: Nutrition & Metabolism
Adam Kassan, Uyen Pham, Quynhmy Nguyen, Melissa E Reichelt, Eunbyul Cho, Piyush M Patel, David M Roth, Brian P Head, Hemal H Patel
Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 over-expression (Cav-3 OE) to study the impact of Cav-3 in regulation of autophagy...
October 5, 2016: American Journal of Physiology. Cell Physiology
Paula Mera, Kathrin Laue, Jianwen Wei, Julian Meyer Berger, Gerard Karsenty
OBJECTIVE: A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age. METHODS: We examined muscle mass and strength in mice lacking osteocalcin (Ocn-/-) or its receptor in all cells (Gprc6a-/-) or specifically in myofibers (Gprc6a Mck -/-) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days...
October 2016: Molecular Metabolism
William J Smiles, Evelyn B Parr, Vernon G Coffey, Orly Lacham-Kaplan, John A Hawley, Donny M Camera
Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise...
September 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
Karen Vignale, Justina V Caldas, Judy A England, Nirun Boonsinchai, Andrew Magnuson, Erik D Pollock, Sami Dridi, Casey M Owens, Craig N Coon
A study was conducted to evaluate the effect of white striping ( WS: ) of broiler breast muscle (Pectoralis major) on protein turnover and gene expression of genes related to protein degradation and fatty acid synthesis. A total of 560 day-old male broiler chicks Cobb 500 were allocated in a total of 16 pens, 35 chicks per pen. A completely randomized design was conducted with a 2 × 3 factorial arrangement (2 scores: severe and normal, and 3 breast meat samples sites). At d 60, 20 birds were randomly selected, euthanized, and scored for white striping...
September 24, 2016: Poultry Science
T Lam, R Harmancey, H Vasquez, B Gilbert, N Patel, V Hariharan, A Lee, M Covey, H Taegtmeyer
We have previously observed the reversal of lipid droplet deposition in skeletal muscle of morbidly obese patients following bariatric surgery. We now investigated whether activation of autophagy is the mechanism underlying this observation. For this purpose, we incubated rat L6 myocytes over a period of 6 days with long-chain fatty acids (an equimolar, 1.0 mM, mixture of oleate and palmitate in the incubation medium). At day 6, the autophagic inhibitor (bafilomycin A1, 200 nM) and the autophagic activator (rapamycin, 1 μM) were added separately or in combination for 48 h...
2016: Cell Death Discovery
Supreeth S Rudrappa, Daniel J Wilkinson, Paul L Greenhaff, Kenneth Smith, Iskandar Idris, Philip J Atherton
The ever increasing burden of an aging population and pandemic of metabolic syndrome worldwide demands further understanding of the modifiable risk factors in reducing disability and morbidity associated with these conditions. Disuse skeletal muscle atrophy (sometimes referred to as "simple" atrophy) and insulin resistance are "non-pathological" events resulting from sedentary behavior and periods of enforced immobilization e.g., due to fractures or elective orthopedic surgery. Yet, the processes and drivers regulating disuse atrophy and insulin resistance and the associated molecular events remain unclear-especially in humans...
2016: Frontiers in Physiology
Jared M Dickinson, Paul T Reidy, David M Gundermann, Michael S Borack, Dillon K Walker, Andrew C D'Lugos, Elena Volpi, Blake B Rasmussen
Essential amino acid (EAA) ingestion enhances postexercise muscle protein synthesis, and in particular, the anabolic response of older adults appears sensitive to the quantity of ingested leucine. The effect of leucine ingestion on muscle breakdown following resistance exercise (RE) is less understood. The purpose of this study was to identify the impact of postexercise leucine ingestion on the ubiquitin proteasome and autophagosomal-lysosomal systems following acute RE in older men. Subjects (72±2yr) performed RE and 1h postexercise ingested 10g of EAA containing a leucine quantity similar to quality protein (Control, 1...
September 1, 2016: Journal of Applied Physiology
Jason L Robinson, Scott V Harding, Janet A Brunton, Robert F Bertolo
BACKGROUND: The neonatal methionine requirement must consider not only the high demand for rapid tissue protein expansion but also the demands as the precursor for a suite of critical transmethylation reactions. However, methionine metabolism is inherently complex because upon transferring its methyl group during transmethylation, methionine can be reformed by the dietary methyl donors choline (via betaine) and folate. OBJECTIVE: We sought to determine whether dietary methyl donors contribute to methionine availability for protein synthesis in neonatal piglets...
October 2016: Journal of Nutrition
Yuki Enoki, Hiroshi Watanabe, Riho Arake, Ryusei Sugimoto, Tadashi Imafuku, Yuna Tominaga, Yu Ishima, Shunsuke Kotani, Makoto Nakajima, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Skeletal muscle atrophy, referred to as sarcopenia, is often observed in chronic kidney disease (CKD) patients, especially in patients who are undergoing hemodialysis. The purpose of this study was to determine whether uremic toxins are involved in CKD-related skeletal muscle atrophy. Among six protein-bound uremic toxins, indole containing compounds, indoxyl sulfate (IS) significantly inhibited proliferation and myotube formation in C2C12 myoblast cells. IS increased the factors related to skeletal muscle breakdown, such as reactive oxygen species (ROS) and inflammatory cytokines (TNF-α, IL-6 and TGF-β1) in C2C12 cells...
2016: Scientific Reports
Astrid M H Horstman, Steven W Olde Damink, Annemie M W J Schols, Luc J C van Loon
Cachexia is a significant clinical problem associated with very poor quality of life, reduced treatment tolerance and outcomes, and a high mortality rate. Mechanistically, any sizeable loss of skeletal muscle mass must be underpinned by a structural imbalance between muscle protein synthesis and breakdown rates. Recent data indicate that the loss of muscle mass with aging is, at least partly, attributed to a blunted muscle protein synthetic response to protein feeding. Whether such anabolic resistance is also evident in conditions where cachexia is present remains to be addressed...
2016: Nutrients
W Kyle Mitchell, Daniel J Wilkinson, Bethan E Phillips, Jonathan N Lund, Kenneth Smith, Philip J Atherton
Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life...
July 2016: Advances in Nutrition
John O Ogunbileje, Craig Porter, David N Herndon, Tony Chao, Doaa R Abdelrahman, Anastasia Papadimitriou, Maria Chondronikola, Teresa A Zimmers, Paul T Reidy, Blake B Rasmussen, Labros S Sidossis
Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria...
August 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Philip J Atherton, Paul L Greenhaff, Stuart M Phillips, Sue C Bodine, Christopher M Adams, Charles H Lang
Muscle wasting resulting wholly or in part from disuse represents a serious medical complication that, when prolonged, can increase morbidity and mortality. Although much knowledge has been gained over the past half century, the underlying etiology by which disuse alters muscle proteostasis remains enigmatic. Multidisciplinary and novel methodologies are needed to fill gaps and overcome barriers to improved patient care. The present review highlights seminal concepts from a symposium at Experimental Biology 2016...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
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