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Myostatin human

Banu Kabak, Muaz Belviranli, Nilsel Okudan
Background The purpose of this study was to investigate irisin and myostatin responses to acute high-intensity interval exercise. Materials and methods Ten male professional kick-boxers aged between 18 and 24 years and 10 sedentary males with similar age and body weight participated in the present study. Participants performed 4 × 30-s Wingate test separated with 4 min of rest. Blood samples were taken immediately before and after exercise, and 3 and 6 h of recovery. Results and conclusion At rest, irisin levels were higher in the kick-boxers (p < 0...
March 20, 2018: Hormone Molecular Biology and Clinical Investigation
Xiaoping Su, Kuiqing Cui, Shanshan Du, Hongli Li, Fenghua Lu, Deshun Shi, Qingyou Liu
Myostatin (MSTN), a protein encoded by growth differentiation factor 8 (GDF8), is primarily expressed in skeletal muscle and negatively regulates the development and regeneration of muscle. Accordingly, myostatin-deficient animals exhibit a double-muscling phenotype. The CRISPR/Cas9 system has proven to be an efficient genome-editing tool and has been applied to gene modification in cells from many model organisms such as Drosophila melanogaster, zebrafish, mouse, rat, sheep, and human. Here, we edited the GDF8 gene in fibroblasts and embryos of Debao pig and swamp buffalo using the CRISPR/Cas9 system...
March 19, 2018: In Vitro Cellular & Developmental Biology. Animal
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
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
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
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
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
Andrew C D'Lugos, Shivam H Patel, Jordan C Ormsby, Donald P Curtis, Christopher S Fry, Chad C Carroll, Jared M Dickinson
Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine if prior consumption of the COX-inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle following RE. In a double-blinded, randomized, crossover design, healthy young men (n=8, 25{plus minus}1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength)...
January 11, 2018: Journal of Applied Physiology
Thomas R Cotton, Gerhard Fischer, Xuelu Wang, Jason C McCoy, Magdalena Czepnik, Thomas B Thompson, Marko Hyvönen
Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a latent precursor in muscle and is activated by sequential proteolysis of the pro-domain. To investigate the molecular mechanism by which pro-myostatin remains latent, we have determined the structure of unprocessed pro-myostatin and analysed the properties of the protein in its different forms. Crystal structures and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin site, has significantly reduced activity compared with the mature growth factor and persists as a stable complex that is resistant to the natural antagonist follistatin...
January 12, 2018: EMBO Journal
Ng Shyh-Chang
Wasting of adipose tissue and skeletal muscle is a hallmark of metastatic cancer and a major cause of death. Like patients with cachexia caused by other chronic infections or inflammatory diseases, the cancer subject manifests both malnutrition and metabolic stress. Both carbohydrate utilization and amino acid incorporation are decreased in the muscles of cancer cachexia patients. Cancer cells affect host metabolism in two ways: (a) their own metabolism of nutrients into other metabolites and (b) circulating factors they secrete or induce the host to secrete...
2017: Advances in Experimental Medicine and Biology
Long-Fei Wu, Dong-Cheng Zhu, Bing-Hua Wang, Yi-Hua Lu, Pei He, Yun-Hong Zhang, Hong-Qin Gao, Xiao-Wei Zhu, Wei Xia, Hong Zhu, Xing-Bo Mo, Xin Lu, Lei Zhang, Yong-Hong Zhang, Fei-Yan Deng, Shu-Feng Lei
Myostatin is mainly secreted by skeletal muscle and negatively regulates skeletal muscle growth. However, the roles of myostatin on bone metabolism are still largely unknown. Here, we recruited two large populations containing 6308 elderly Chinese and conducted comprehensive statistical analyses to evaluate the associations among lean body mass (LBM), plasma myostatin, and bone mineral density (BMD). Our data revealed that total myostatin in plasma was mainly determined by LBM. The relative abundance of mature myostatin (mature/total) was significantly lower in high versus low BMD subjects...
December 16, 2017: Journal of Cellular and Molecular Medicine
Katja Walpurgis, Andreas Thomas, Frank Dellanna, Wilhelm Schänzer, Mario Thevis
PURPOSE: Inhibitors of the ActRII signaling pathways represent promising therapeutics for the treatment of muscular diseases, but also pose risks as performance-enhancing agents in sports. Bimagrumab is a human anti-ActRII antibody which was found to increase muscle mass and function by blocking ActRII signaling. As it has considerable potential for being misused as doping agent in sports, the aim of this study was to develop a mass spectrometric detection assay for doping control serum samples...
December 11, 2017: Proteomics. Clinical Applications
Michael St Andre, Mark Johnson, Prashant N Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M Burch, Peter Bialek, Carl Morris, Jane Owens
BACKGROUND: The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice...
November 9, 2017: Skeletal Muscle
Frederic Morvan, Jean-Michel Rondeau, Chao Zou, Giulia Minetti, Clemens Scheufler, Meike Scharenberg, Carsten Jacobi, Pascale Brebbia, Veronique Ritter, Gauthier Toussaint, Claudia Koelbing, Xavier Leber, Alain Schilb, Florian Witte, Sylvie Lehmann, Elke Koch, Sabine Geisse, David J Glass, Estelle Lach-Trifilieff
The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice leads to hypertrophy or prevention of muscle loss, perhaps suggesting that the ActRIIB receptor is primarily responsible for muscle growth regulation...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Kunihiro Sakuma, Akihiko Yamaguchi
Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and often frailty. This review focuses on the recent advances of pharmacological, hormonal, and nutritional approaches for attenuating sarcopenia. The article is composed of the data reported in many basic and some clinical studies for mammalian muscles. Resistance training combined with amino acid-containing supplements is the gold standard to prevent sarcopenia...
October 18, 2017: Pflügers Archiv: European Journal of Physiology
Mette Flindt Heisterberg, Jesper L Andersen, Peter Schjerling, Jacob Bülow, Jeppe Bo Lauersen, Heidi L Roeber, Michael Kjaer, Abigail L Mackey
PURPOSE: To investigate the effect of blocking the angiotensin II type I receptor (AT1R) upon the response to acute heavy resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by downregulation of TGF-β and upregulation of IGF-1 signalling. METHODS: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to exercise...
October 16, 2017: Medicine and Science in Sports and Exercise
Indranil Bhattacharya, Zorayr Manukyan, Phylinda Chan, Anne Heatherington, Lutz Harnisch
Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies suggested that body-weight- and body-surface-area-adjusted clearance and volume of distribution estimates between adults and children are similar for subjects older than 6 years. Population modeling identified a Michaelis-Menten binding kinetics model to optimally characterize the target mediated drug disposition profile of domagrozumab and identified body mass index on the volume of distribution as the only significant covariate...
October 12, 2017: Journal of Clinical Pharmacology
Carla Vermeulen Carvalho Grade, Carolina Stefano Mantovani, Marina Alves Fontoura, Faisal Yusuf, Beate Brand-Saberi, Lúcia Elvira Alvares
Myostatin (MSTN) is a strong inhibitor of skeletal muscle growth in human and other vertebrates. Its transcription is controlled by a proximal promoter/enhancer (Mstn P/E) containing a TATA box besides CREB, NF-Y, MEIS1 and FXR transcription factor binding sites (TFBSs), which are conserved throughout evolution. The aim of this work was to investigate the role of these TFBSs on Mstn P/E activity and evaluate the potential of their putative ligands as Mstn trans regulators. Mstn P/E mutant constructs were used to establish the role of conserved TFBSs using dual-luciferase assays...
October 2017: Molecular Biology Reports
Shehla Pervin, Vineeta Singh, Alexandria Tucker, Javier Collazo, Rajan Singh
Obesity is a major risk factor for the development of diabetes, insulin resistance, dyslipidemia, cardiovascular disease and other related metabolic conditions. Obesity develops from perturbations in overall cellular bioenergetics when energy intake chronically exceeds total energy expenditure. Lifestyle interventions based on reducing total energy uptake and increasing activities including exercise have proved ineffective in the prevention and treatment of obesity because of poor adherence to such interventions for an extended period of time...
September 9, 2017: Hormone Molecular Biology and Clinical Investigation
Charlotte Suetta
In order to study the influence of disuse and aging on skeletal muscle homeostasis, different human models were employed. Effects of chronic disuse were investigated in elderly patients suffering from uni-lateral hip-osteoarthritis, whereas the effect of short-term disuse (4 and 14 days of unilateral lower limb immobilisation) was assessed in healthy young and old individuals. In summary, chronic muscle disuse in the elderly was associated with marked quantitative as well as qualitative neuromuscular impairments...
August 2017: Danish Medical Journal
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