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myostatin inhibitor

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
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
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
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
Anil C Anand
As the cirrhosis progresses, development of complication like ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma signify increasing risk of short term mortality. Malnutrition and muscle wasting (sarcopenia) is yet other complications that negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Conventionally, these are not routinely looked for, because nutritional assessment can be a difficult especially if there is associated fluid retention and/or obesity...
December 2017: Journal of Clinical and Experimental Hepatology
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
Luce Périè, Alexis Parenté, Fabienne Baraige, Laetitia Magnol, Véronique Blanquet
BACKGROUND/AIMS: Myostatin is known as a powerful negative regulator of muscle growth playing a key role in skeletal muscle homeostasis. Recent studies revealed that myostatin-deficient mice lead to an increase of insulin sensitivity, a decrease of adiposity and a resistance to obesity, showing that myostatin can also impact on metabolism. Thus, myostatin appeared as a potential therapeutic target to treat insulin resistance. METHODS: We generated transgenic mice overexpressing Gasp-1, a myostatin inhibitor...
2017: Cellular Physiology and Biochemistry
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
Ki-Young Kim, Sae-Kwang Ku, Ki-Won Lee, Chang-Hyun Song, Won G An
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandrae Fructus (SF), the dried fruit of Schisandra chinensis (Turcz.) Baill., is a well-known traditional herb used in Asia for enhancing physical work capacity as well as providing anti-stress and anti-inflammatory effects. Extracts of SF (SFe) have also been reported to increase skeletal muscle mass and inhibit muscle atrophy. AIM OF THE STUDY: We examined whether SFe had muscle-protective effects in old mice after chronic forced exercises, and, if so, relevant mechanisms...
October 28, 2017: Journal of Ethnopharmacology
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
Eric Marty, Yi Liu, Andre Samuel, Omer Or, Joseph Lane
Sarcopenia is defined as an age associated decline in skeletal muscle mass. The pathophysiology of sarcopenia is multifactorial, with decreased caloric intake, muscle fiber denervation, intracellular oxidative stress, hormonal decline, and enhanced myostatin signaling all thought to contribute. Prevalence rates are as high as 29% and 33% in elderly community dwelling and long-term care populations, respectively, with advanced age, low body mass index, and low physical activity as significant risk factors. Sarcopenia shares many characteristics with other disease states typically associated with risk of fall and fracture, including osteoporosis, frailty, and obesity...
December 2017: Bone
Christoph Wallner, Henriette Jaurich, Johannes Maximilian Wagner, Mustafa Becerikli, Kamran Harati, Mehran Dadras, Marcus Lehnhardt, Björn Behr
Metabolic diseases like diabetes mellitus cause bone healing deficiencies. We found significant impairment of bone regeneration, osteogenic differentiation and proliferation in diabetic bone. Moreover recent studies suggest a highly underestimated importance of GDF8 (Myostatin) in bone metabolism. Our goal was to analyze the role of GDF8 as a regulator of osteogenic differentiation, proliferation and bone regeneration. We used a murine tibial defect model in diabetic (Lepr(db-/-)) mice. Myostatin-Inhibitor Follistatin was administered in tibial bony defects of diabetic mice...
August 29, 2017: Scientific Reports
Caroline Barbé, Fabrice Bray, Marine Gueugneau, Stéphanie Devassine, Pascale Lause, Caroline Tokarski, Christian Rolando, Jean-Paul Thissen
Skeletal muscle, the most abundant body tissue, plays vital roles in locomotion and metabolism. Myostatin is a negative regulator of skeletal muscle mass. In addition to increasing muscle mass, Myostatin inhibition impacts muscle contractility and energy metabolism. To decipher the mechanisms of action of the Myostatin inhibitors, we used proteomic and transcriptomic approaches to investigate the changes induced in skeletal muscles of transgenic mice overexpressing Follistatin, a physiological Myostatin inhibitor...
October 6, 2017: Journal of Proteome Research
Natalie J Offord, Miles D Witham
Sarcopenia refers to the loss of muscle mass and strength seen with advancing age. The pathophysiology is multifactorial, with loss of muscle satellite cells, changes in hormonal systems, chronic inflammation, oxidative stress and anabolic resistance to protein utilisation all implicated. Older age, female sex and immobility are important risk factors. Sarcopenia is clinically important as it is a major risk factor for physical frailty, falls, prolonged hospitalisation, dependency and earlier death. Diagnosis requires evidence of reduced muscle mass measured by handgrip strength or walk speed, together with evidence of low muscle mass, measured by one of a variety of techniques such as bioimpedance analysis or dual X-ray absorptiometry...
July 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
Peter P Nghiem, Joe N Kornegay, Kitipong Uaesoontrachoon, Luca Bello, Ying Yin, Akanchha Kesari, Priya Mittal, Scott J Schatzberg, Gina M Many, Norman H Lee, Eric P Hoffman
INTRODUCTION: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN). METHODS: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were employed in myogenic cells and the mdx mouse treated with recombinant mouse (rm) or human (Hu) OPN protein. RESULTS: OPN was increased and MSTN was decreased and levels correlated inversely in GRMD hypertrophied muscle...
December 2017: Muscle & Nerve
Yuko Ono, Kazuho Sakamoto
BACKGROUND: Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or with various endogenous diseases that are associated with metabolic endotoxemia. Involuntary loss of skeletal muscle, termed muscle wasting, is commonly observed in these conditions, suggesting that circulating LPS might play an essential role in its development. Although impairment of muscle regeneration is an important determinant of skeletal muscle wasting, it is unclear whether LPS affects this process and, if so, by what mechanism...
2017: PloS One
Kentaro Takayama, Cédric Rentier, Tomo Asari, Akari Nakamura, Yusuke Saga, Takahiro Shimada, Kei Nirasawa, Eri Sasaki, Kyohei Muguruma, Akihiro Taguchi, Atsuhiko Taniguchi, Yoichi Negishi, Yoshio Hayashi
Myostatin, a negative regulator of skeletal muscle growth, is a promising target for treating muscle atrophic disorders. Recently, we discovered a minimal myostatin inhibitor 1 (WRQNTRYSRIEAIKIQILSKLRL-amide) derived from positions 21-43 of the mouse myostatin prodomain. We previously identified key residues (N-terminal Trp(21), rodent-specific Tyr(27), and all aliphatic amino acids) required for effective inhibition through structure-activity relationship (SAR) studies based on 1 and characterized a 3-fold more potent inhibitor 2 bearing a 2-naphthyloxyacetyl group at position 21...
July 13, 2017: ACS Medicinal Chemistry Letters
Mohammad Hassan Baig, Arif Tasleem Jan, Gulam Rabbani, Khurshid Ahmad, Jalaluddin M Ashraf, Taeyeon Kim, Han Sol Min, Yong Ho Lee, Won-Kyung Cho, Jin Yeul Ma, Eun Ju Lee, Inho Choi
Methylglyoxal (MG) is a reactive dicarbonyl intermediate and a precursor of advanced glycation end products (AGEs). The authors investigated the role played by AGEs in muscle myopathy and the amelioration of its effects by curcumin and gingerol. In addition to producing phenotypical changes, MG increased oxidative stress and reduced myotube formation in C2C12 cells. RAGE (receptor for AGEs) expression was up-regulated and MYOD and myogenin (MYOG) expressions were concomitantly down-regulated in MG-treated cells...
July 19, 2017: Scientific Reports
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