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Rishibha Sachdev, Karin Kappes-Horn, Lydia Paulsen, Yvonne Duernberger, Catharina Pleschka, Philip Denner, Bishwajit Kundu, Jens Reimann, Ina Vorberg
Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line...
March 15, 2018: Molecular Neurobiology
Shuping Yang, Xin Li, Xinfeng Liu, Xiangbin Ding, Xiangbo Xin, Congfei Jin, Sheng Zhang, Guangpeng Li, Hong Guo
MSTN -encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis...
February 16, 2018: Oncotarget
Ifigeneia Kalampouka, Angel van Bekhoven, Bradley T Elliott
Ageing is associated with a general reduction of physiological function and a reduction of muscle mass and strength. Endocrine factors such as myostatin, activin A, growth and differentiation factor 11 (GDF-11) and their inhibitory peptides influence muscle mass in health and disease. We hypothesised that myocytes cultured in plasma from older and younger individuals would show an ageing effect, with reduced proliferation and differentiation in older environments. C2C12 myoblasts were grown as standard and stimulated with media conditioned with 5% plasma from healthy male participants that were either younger ( n = 6, 18-35 years of age) or older ( n = 6, >57 years of age)...
2018: Frontiers in Physiology
Hisashi Kato, Shinya Masuda, Tomotaka Ohira, Luna Ohira, Hisashi Takakura, Yoshinobu Ohira, Tetsuya Izawa
β-Guanidinopropionic acid (β-GPA) feeding inhibits growth-associated gain of body mass. It remains unknown, however, whether and how β-GPA feeding affects growth-associated increase in white adipose tissue (WAT) mass. We examined the effects of 4- and 8-week β-GPA feeding on serum myostatin levels and expression of genes and proteins related to adipogenesis, lipolysis, and liposynthesis in epididymal WAT (eWAT) and brown adipose tissue (BAT) in 3-week-old, juvenile male mice. Body, eWAT, and muscle weights were significantly lower in β-GPA-fed mice than in controls after feeding...
March 2018: Physiological Reports
Agata Bielecka-Dabrowa, Jarosław Fabis, Dimitri P Mikhailidis, Stephan von Haehling, Amirhossein Sahebkar, Jacek Rysz, Maciej Banach
Some studies using small doses of statins revealed significant benefits for patients with chronic heart failure (HF). However, the results of large randomized studies did not confirm these advantages. Along with the primary effect of cholesterol lowering, statins have many ancillary actions that may be relevant for body wasting. In this context, the fear of muscle-related side effects needs to be put into clinical context and assessed appropriately before statins are either withheld or withdrawn in patients with sarcopenia (muscle wasting)...
March 1, 2018: Trends in Pharmacological Sciences
Meixia Pang, Jingou Tong, Xiaomu Yu, Beide Fu, Ying Zhou
Follistatin (FST) is a single-chain gonadal protein involving in various biological effects. FST plays important roles in not only ovary development but also body growth, whereas myostatin (MSTN) negatively regulates muscle growth. In this study, FST gene in bighead carp (HynFST) was cloned and characterized. A 5797 bp genomic sequence of HynFST, consisting six exons and five introns were cloned. The full-length cDNA of HynFST (2134 bp) has an open reading fragment encoding a polypeptide of 349 amino acids...
February 26, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Yufeng Zhang, Kang Nian Yap, Tony D Williams, David L Swanson
Skeletal muscle remodeling is an important component of phenotypic flexibility in birds and impacts organismal metabolism and performance, which could potentially influence fitness. One regulator of skeletal muscle remodeling is myostatin, an autocrine/paracrine muscle growth inhibitor that may be down-regulated under conditions promoting heavier muscle masses. In this study, we employed protocols requiring hovering while foraging to increase foraging costs and modify phenotypes of zebra finches (Taeniopygia guttata)...
May 2018: Physiological and Biochemical Zoology: PBZ
Yufeng Zhang, Kathleen Eyster, David L Swanson
A prominent example of seasonal phenotypic flexibility is the winter increase in thermogenic capacity (=summit metabolism, [Formula: see text]) in small birds, which is often accompanied by increases in pectoralis muscle mass and lipid catabolic capacity. Temperature or photoperiod may be drivers of the winter phenotype, but their relative impacts on muscle remodeling or lipid transport pathways are little known. We examined photoperiod and temperature effects on pectoralis muscle expression of myostatin, a muscle growth inhibitor, and its tolloid-like protein activators (TLL-1 and TLL-2), and sarcolemmal and intracellular lipid transporters in dark-eyed juncos Junco hyemalis ...
February 2018: Current Zoology
Chad E Glasser, Michael R Gartner, Dawn Wilson, Barry Miller, Matthew L Sherman, Kenneth M Attie
INTRODUCTION: ACE-083 is a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first-in-human study examined these effects. METHODS: In this phase 1, randomized, double-blind, placebo-controlled, dose-ranging study in healthy postmenopausal women, ACE-083 (50-200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart...
February 27, 2018: Muscle & Nerve
Justin R Fallon, Elizabeth M McNally
The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration...
February 23, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
A Bedford, H Yu, M Hernandez, E J Squires, S Leeson, J Gong
Butyric acid is the primary energy source for colonocytes, and has shown potential as an alternative to in-feed antibiotics, due to its antimicrobial activity and positive effects on production performance traits of broiler chickens. SILOhealth 104 (SILO S.P.A., Florence, Italy) is a commercial product mainly containing mono- and di-glycerides of butyrate with a small portion of propionic, caprylic, capric, and lauric acid mono- and di-glycerides. Its effects on broiler performance and carcass composition have yet to be evaluated...
February 14, 2018: Poultry Science
Xu Zhou, Daijiao Yi, Yanhong Wu, Xinghua Pei, Haiming Yu, Yanhong Chen, Yu Jiang, Wenpu Li
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function. The present study aimed to investigate the diaphragmatic protein expression of myostatin and its correlation with apoptosis in a rat model of CPOD. Sprague Dawley rats were randomly divided into a control group and a COPD group, the latter of which were exposed to cigarette smoke to build a rat model of COPD. The validity of the COPD model was evaluated by assessment of lung function and histopathological analysis...
March 2018: Experimental and Therapeutic Medicine
Danielle De Lima Rodrigues, Agnelo Neves Alves, Beatriz Ribeiro Guimarães, Weslley Wallace de Alcântara Araujo Amorim, Sandra Kalil Bussadori, Kristianne Porta Santos Fernandes, Raquel Agnelli Mesquita-Ferrari
The aim of the present study was to evaluate the effects of LLLT prior to muscle injury with and without post-injury irradiation on the expression of isoforms of myosin heavy chain (MyHC), calcineurin (CaN), and myostatin during the repair process. Wistar rats were divided into five groups: control (n = 7); injury (n = 21); LLLT + injury (n = 21); injury + LLLT (n = 21), and LLLT + injury + LLLT (n = 21). Cryoinjury was performed on the tibialis anterior (TA) muscle. The injured groups were euthanized at 3, 7, and 14 days after injury...
February 15, 2018: Lasers in Medical Science
Freddy J K Toloza, Jose O Mantilla-Rivas, Maria C Pérez-Matos, Maria L Ricardo-Silgado, Martha C Morales-Alvarez, Jairo A Pinzón-Cortés, Maritza Pérez-Mayorga, Martha L Arévalo-Garcia, Giovanni Tolosa-González, Carlos O Mendivil
Background: Myokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines [myonectin, myostatin, and fibroblast-derived growth factor 21 (FGF-21)] would be associated with direct and indirect indicators of insulin resistance (IR) in individuals who did not have a diagnosis of diabetes...
2018: Frontiers in Endocrinology
Anita Kneppers, Lex Verdijk, Chiel de Theije, Mark Corten, Ellis Gielen, Luc van Loon, Annemie Schols, Ramon Langen
BACKGROUND: Due to the post-mitotic nature of myonuclei, postnatal myogenesis is essential for skeletal muscle growth, repair, and regeneration. This process is facilitated by satellite cells through proliferation, differentiation, and subsequent fusion with a pre-existing muscle fiber (i.e., myonuclear accretion). Current knowledge of myogenesis is primarily based on the in vitro formation of syncytia from myoblasts, which represents aspects of developmental myogenesis, but may incompletely portray postnatal myogenesis...
February 14, 2018: Skeletal Muscle
Pim Knuiman, Maria T E Hopman, Jeroen A Wouters, Marco Mensink
Background: Substantial research has been done on the impact of carbohydrate and fat availability on endurance exercise adaptation, though its role in the acute adaptive response to resistance exercise has yet to be fully characterized. Purpose: We aimed to assess the effects of a pre-resistance exercise isocaloric mixed meal containing different amounts of carbohydrates and fat, on post-resistance exercise gene expression associated with muscle adaptation. Methods: Thirteen young (age 21.2 ± 1.6 year), recreationally trained (VO2max 51...
2018: Frontiers in Physiology
L A Consitt, B C Clark
The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed 'sarcopenic obesity', contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics...
2018: Journal of Frailty & Aging
Wei Le, Andre Eu-Jin Cheah, Jeffrey Yao
BACKGROUND: To investigate the effect of myostatin (GDF-8) stimulation of bone marrow derived mesenchymal stem cells (BMSCs) on tenogenesis in the setting of tendon repair. GDF-8 has demonstrated the ability to augment tenogenesis and we sought to identify if this effect could lead to the focused differentiation of pluripotential stem cells down a tenocyte lineage ex vivo. METHODS: Cadaveric upper limb flexor tendons were harvested, decellularized and divided into 1 cm segments...
March 2018: Journal of Hand Surgery Asian-Pacific Volume
B A Freking, D A King, S D Shackelford, T L Wheeler, T P L Smith
Objectives were to document effects of the Texel myostatin mutation (MSTN) on growth and carcass traits and also test whether or not interactions with the callipyge mutation (CLPG) could be detected. Twelve rams heterozygous at both loci on the two different chromosomes were mated to 215 terminal-sire type composite crossbred ewes genotyped as non-carriers for both loci. A total of 365 lambs were born, 362 of those were genotyped and 236 lambs contributed carcass data to estimate effects and interactions among the four genotype combinations produced...
February 1, 2018: Journal of Animal Science
M Pirruccello-Straub, J Jackson, S Wawersik, M T Webster, L Salta, K Long, W McConaughy, A Capili, C Boston, G J Carven, N K Mahanthappa, K J Turner, A Donovan
Many growth factors are intimately bound to the extracellular matrix, with regulated processing and release leading to cellular stimulation. Myostatin and GDF11 are closely related members of the TGFβ family whose activation requires two proteolytic cleavages to release the growth factor from the prodomain. Specific modulation of myostatin and GDF11 activity by targeting growth factor-receptor interactions has traditionally been challenging. Here we demonstrate that a novel strategy for blocking myostatin and GDF11, inhibition of growth factor release, specifically and potently inhibits signaling both in vitro and in vivo...
February 2, 2018: Scientific Reports
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