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Muscle-skeletal chains

Tomonori Sato, Yoshiaki Ito, Takashi Nagasawa
Sarcopenia is a condition of the loss of muscle mass that is associated with aging and that increases the risk for bedridden state, thereby warranting studies of interventions that attenuate sarcopenia. Here the effects of 2-month dietary L-lysine (Lys) supplementation (1.5-3.0 %) on myofibrillar protein degradation and major proteolytic systems were investigated in senescence-accelerated mouse prone 8 (SAMP8). At 36 weeks of age, skeletal muscle and lean body mass was reduced in SAMP8 when compared with control senescence-accelerated mouse resistant 1 (SAMR1)...
October 17, 2016: Biogerontology
Mayra de A Marques, Guilherme A P de Oliveira
Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the "disease of the sarcomere...
2016: Frontiers in Physiology
Laís Rosa Viana, Rafael Canevarolo, Anna Caroline Perina Luiz, Raquel Frias Soares, Camila Lubaczeuski, Ana Carolina de Mattos Zeri, Maria Cristina Cintra Gomes-Marcondes
BACKGROUND: Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia)...
October 3, 2016: BMC Cancer
Amir Mizbani, Edlira Luca, Elisabeth J Rushing, Jan Krützfeldt
MicroRNAs (miRNAs) are important regulators of skeletal muscle regeneration, but the underlying mechanisms are still incompletely understood. Here, comparative miRNA sequencing analysis of myogenic progenitor cells (MPs) and non-myogenic fibroblast-adipocyte progenitors (FAPs) during cardiotoxin (CTX)-induced muscle injury uncovered miR-501 as a novel muscle-specific miRNA. miR-501 is an intronic miRNA and its expression levels in MPs correlated with its host gene, chloride channel, voltage-sensitive 5, Clcn5 Pharmacological inhibition of miR-501 dramatically blunted the induction of embryonic myosin heavy chain (MYH3) and, to a lesser extent, adult myosin isoforms during muscle regeneration and promoted small-diameter neofibers...
October 5, 2016: Development
Jonathan Shintaku, Jennifer M Peterson, Erin E Talbert, Jin-Mo Gu, Katherine J Ladner, Dustin R Williams, Kambiz Mousavi, Ruoning Wang, Vittorio Sartorelli, Denis C Guttridge
MyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets, including PGC-1β, a master regulator of mitochondrial biogenesis...
October 4, 2016: Cell Reports
Kelsey A Thomas, Michael C Gibbons, John G Lane, Anshuman Singh, Samuel R Ward, Adam J Engler
Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears...
October 4, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Monika Oláhová, Kyle Thompson, Steven A Hardy, Inês A Barbosa, Arnaud Besse, Maria-Eleni Anagnostou, Kathryn White, Tracey Davey, Michael A Simpson, Michael Champion, Greg Enns, Susan Schelley, Robert N Lightowlers, Zofia M A Chrzanowska-Lightowlers, Robert McFarland, Charu Deshpande, Penelope E Bonnen, Robert W Taylor
Mitochondrial diseases collectively represent one of the most heterogeneous group of metabolic disorders. Symptoms can manifest at any age, presenting with isolated or multiple-organ involvement. Advances in next-generation sequencing strategies have greatly enhanced the diagnosis of patients with mitochondrial disease, particularly where a mitochondrial aetiology is strongly suspected yet OXPHOS activities in biopsied tissue samples appear normal. We used whole exome sequencing (WES) to identify the molecular basis of an early-onset mitochondrial syndrome-pathogenic biallelic variants in the HTRA2 gene, encoding a mitochondria-localised serine protease-in five subjects from two unrelated families characterised by seizures, neutropenia, hypotonia and cardio-respiratory problems...
September 30, 2016: Journal of Inherited Metabolic Disease
Leslie A Consitt, Timothy R Koves, Deborah M Muoio, Masato Nakazawa, Christopher A Newton, Joseph A Houmard
The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation...
October 28, 2016: Biochemical and Biophysical Research Communications
Kyle Thompson, Homa Majd, Christina Dallabona, Karit Reinson, Martin S King, Charlotte L Alston, Langping He, Tiziana Lodi, Simon A Jones, Aviva Fattal-Valevski, Nitay D Fraenkel, Ann Saada, Alon Haham, Pirjo Isohanni, Roshni Vara, Inês A Barbosa, Michael A Simpson, Charu Deshpande, Sanna Puusepp, Penelope E Bonnen, Richard J Rodenburg, Anu Suomalainen, Katrin Õunap, Orly Elpeleg, Ileana Ferrero, Robert McFarland, Edmund R S Kunji, Robert W Taylor
Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations...
October 6, 2016: American Journal of Human Genetics
Carles Lerin, Allison B Goldfine, Tanner Boes, Manway Liu, Simon Kasif, Jonathan M Dreyfuss, Ana Luisa De Sousa-Coelho, Grace Daher, Irini Manoli, Justin R Sysol, Elvira Isganaitis, Niels Jessen, Laurie J Goodyear, Kirk Beebe, Walt Gall, Charles P Venditti, Mary-Elizabeth Patti
OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0...
October 2016: Molecular Metabolism
Anabel Martinez Lyons, Anna Ardissone, Aurelio Reyes, Alan J Robinson, Isabella Moroni, Daniele Ghezzi, Erika Fernandez-Vizarra, Massimo Zeviani
BACKGROUND: Assembly of cytochrome c oxidase (COX, complex IV, cIV), the terminal component of the mitochondrial respiratory chain, is assisted by several factors, most of which are conserved from yeast to humans. However, some of them, including COA7, are found in humans but not in yeast. COA7 is a 231aa-long mitochondrial protein present in animals, containing five Sel1-like tetratricopeptide repeat sequences, which are likely to interact with partner proteins. METHODS: Whole exome sequencing was carried out on a 19 year old woman, affected by early onset, progressive severe ataxia and peripheral neuropathy, mild cognitive impairment and a cavitating leukodystrophy of the brain with spinal cord hypotrophy...
September 28, 2016: Journal of Medical Genetics
Takeshi Shimoide, Naoyuki Kawao, Yukinori Tamura, Hironobu Morita, Hiroshi Kaji
Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions...
October 21, 2016: Biochemical and Biophysical Research Communications
Noritada Yoshikawa, Noriaki Shimizu, Masaaki Uehara, Aya Oda, Ryo Matsumiya, Erika Matsubara, Hiroshi Kobayashi, Osamu Hosono, Akiko Kuribara-Souta, Hiroyuki Baba, Fumitaka Nagamura, Shigeru Kiryu, Hirotoshi Tanaka
OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC). METHODS: Patients with rheumatic disorders treated with prednisolone (≥10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross-sectional area of mid-thigh muscle...
September 28, 2016: Modern Rheumatology
Andrew C Fry, Terry J Housh, Joel B Cramer, Joseph P Weir, Travis W Beck, Brian K Schilling, Jonathan D Miller, Justin X Nicoll
Numerous conditions and types of physical activity (e.g., exercise, aging, muscle-related diseases) can influence muscle fiber types and the proteins expressed. To date, muscle fibers can only be characterized by actually obtaining a tissue sample using the invasive muscle biopsy procedure. Mechanomyography (MMG) is the assessment of the vibration properties of contracting skeletal muscle, and has been proposed as a possible non-invasive method for muscle fiber analysis. Therefore, the purpose of this project was to examine the feasibility of using MMG and muscle performance measures to non-invasively assess muscle fiber characteristics...
September 20, 2016: Journal of Strength and Conditioning Research
Amy E Vincent, Hannah S Rosa, Charlotte L Alston, John P Grady, Karolina A Rygiel, Mariana C Rocha, Rita Barresi, Robert W Taylor, Doug M Turnbull
Dysferlinopathies are caused by mutations in the DYSF gene and patients may present with proximal or distal myopathy. Dysferlin is responsible for membrane resealing, and mutations may result in a defect in membrane repair following mechanical or chemical stress, causing an influx of Ca(2+). Since mitochondria are involved in Ca(2+) buffering, we hypothesised that mitochondrial defects may be present in skeletal muscle biopsies from patients with mutations in this gene. The aim was to characterise mitochondrial defects in muscle from patients with dysferlinopathies...
August 29, 2016: Neuromuscular Disorders: NMD
Xiaoxi Zhu, Melanie Kny, Franziska Schmidt, Alexander Hahn, Tobias Wollersheim, Christian Kleber, Steffen Weber-Carstens, Jens Fielitz
OBJECTIVE: In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-β1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-β1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled-related protein 2 reduction enhances transforming growth factor-β1-mediated effects and investigated the interrelationship between transforming growth factor-β1 and secreted frizzled-related protein 2 in inflammation-induced atrophy...
September 21, 2016: Critical Care Medicine
Bruce A Young, Jessica Dumais, Nicholas John, Brandon Lyons, Andrew Macduff, Matthew Most, Nathan A Reiser, Peter J Reiser
Water monitor lizards (Varanus salvator) swim using sinusoidal oscillations generated at the base of their long (50% of total body length) tail. In an effort to determine which level of the structural/organizational hierarchy of muscle is associated with functional segregation between the muscles of the tail base, an array of muscle features-myosin heavy chain profiles, enzymatic fiber types, twitch and tetanic force production, rates of fatigue, muscle compliance, and electrical activity patterns-were quantitated...
2016: Frontiers in Physiology
G Xu, J S Hansen, X J Zhao, S Chen, M Hoene, X L Wang, J O Clemmesen, N H Secher, H U Häring, B K Pedersen, R Lehmann, C Weigert, P Plomgaard
BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise in humans. METHODS: In two independent studies young healthy males fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n=9) or the flux over the hepato-splanchnic bed (n=10)...
September 20, 2016: Journal of Clinical Endocrinology and Metabolism
Bruno G Teodoro, Igor H Sampaio, Lucas H M Bomfim, André L Queiroz, Leonardo R Silveira, Anderson O Souza, Anna M A P Fernandes, Marcos N Eberlin, Tai-Yu Huang, Donghai Zheng, P Darrell Neufer, Ronald N Cortright, Luciane C Alberici
Long-chain Acyl-CoA Synthetases (ACSL 1 to 6) are key enzymes regulating partitioning of acyl-CoA species toward different metabolic fates such as lipid synthesis or β-oxidation. Despite the understanding that ecotopic lipid accumulation in skeletal muscle is associated with metabolic diseases like obesity and Type II Diabetes, the role of specific ACSL isoforms in lipid synthesis remains unclear. Herein we describe for the first time the presence of ACSL6 mRNA in human skeletal muscle and the role that ACSL6 plays in lipid synthesis in both rodent and human skeletal muscle...
September 20, 2016: Journal of Physiology
Jeong-Seok Kim, Young-Hee Lee, Ho-Keun Yi
Recent evidence suggests that autophagy and bone morphogenetic protein signaling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups; young (YC) and late middle-aged (LMC), and two types of running training groups: late middle-aged downhill (LMD) and late middle-aged uphill (LMU)...
September 19, 2016: Experimental Physiology
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