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https://www.readbyqxmd.com/read/29348202/molecular-characterization-of-latent-gdf8-reveals-mechanisms-of-activation
#1
Ryan G Walker, Jason C McCoy, Magdalena Czepnik, Melanie J Mills, Adam Hagg, Kelly L Walton, Thomas R Cotton, Marko Hyvönen, Richard T Lee, Paul Gregorevic, Craig A Harrison, Thomas B Thompson
Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is "spring-loaded...
January 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343545/tolloid-cleavage-activates-latent-gdf8-by-priming-the-pro-complex-for-dissociation
#2
Viet Q Le, Roxana E Iacob, Yuan Tian, William McConaughy, Justin Jackson, Yang Su, Bo Zhao, John R Engen, Michelle Pirruccello-Straub, Timothy A Springer
Growth differentiation factor 8 (GDF8)/myostatin is a latent TGF-β family member that potently inhibits skeletal muscle growth. Here, we compared the conformation and dynamics of precursor, latent, and Tolloid-cleaved GDF8 pro-complexes to understand structural mechanisms underlying latency and activation of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro-complexes reveals a V-shaped conformation that is unaltered by furin cleavage and sharply contrasts with the ring-like, cross-armed conformation of latent TGF-β1...
January 17, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29340059/microrna-95-promotes-myogenic-differentiation-by-down-regulation-of-aminoacyl-trna-synthase-complex-interacting-multifunctional-protein-2
#3
Biao Li, Shanshan Xie, Chunbo Cai, Lili Qian, Shengwang Jiang, Dezun Ma, Gaojun Xiao, Ting Gao, Jinzeng Yang, Wentao Cui
MicroRNA-95 (miR-95) is well known for its ability to promote the proliferation of a variety of cancer cells, but its function in skeletal muscle development has not been reported so far. Our laboratory has recently generated genetically engineered Meishan pigs containing a loss-of-function myostatin (MSTN) mutant (MSTN-/-). These MSTN-/- pigs grow and develop normally but show clear double muscle phenotype as observed in Belgian cattle. We observed that the expression of miR-95 was up-regulated in the longissimus dorsi from MSTN-/- Meishan pigs at day 65 during embryo development...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29330193/structure-of-the-human-myostatin-precursor-and-determinants-of-growth-factor-latency
#4
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
https://www.readbyqxmd.com/read/29308681/therapeutic-considerations-of-sarcopenia-in-heart-failure-patients
#5
Masakazu Saitoh, Nicole Ebner, Stephan von Haehling, Stefan D Anker, Jochen Springer
Sarcopenia is a common feature, and affects 20-47% of patients with heart failure (HF). Sarcopenia is also an independent predictor of impaired functional capacity, even after adjusting for clinical relevant variables, which is associated with adverse outcome in patients with HF. Areas covered: Several different pathophysiological pathways are involved in sarcopenic processes including altered nutrient intake and absorption, hormonal factor, inflammatory processes, oxidative stress, cellular proteolysis, and unhealthy lifestyle...
January 7, 2018: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29288571/early-second-trimester-maternal-serum-markers-in-prediction-of-gestational-diabetes-mellitus
#6
Baihui Zhao, Xiujun Han, Qing Meng, Qiong Luo
AIMS: To determine whether maternal serum markers in the early-second trimester are useful for prediction of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 876 singleton pregnancies were recruited in the present study. Blood samples were collected during 16-20 gestational weeks. GDM women were diagnosed by OGTT during 24-28 gestational weeks. Fifty-six cases of GDM and 73 healthy cases were selected. Maternal serum concentrations of placental protein 13 (PP13), pentraxin 3 (PTX3), soluble fms-like tyrosine kinase-1 (sFlt-1), myostatin and follistatin (FST) were detected at 16-20 weeks' gestation...
December 29, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29282687/metabolic-changes-during-cancer-cachexia-pathogenesis
#7
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
https://www.readbyqxmd.com/read/29277394/nitric-oxide-treatment-attenuates-muscle-atrophy-during-hind-limb-suspension-in-mice
#8
Judy E Anderson, Antonia Zhu, Tooru M Mizuno
Debilitating muscle-disuse atrophy in aging or obesity i has huge socioeconomic impact. Since nitric oxide (NO) mediates muscle satellite cell activation and induces hypertrophy with exercise in old mice, we tested whether treatment with the NO donor, isosorbide dinitrate (ISDN), during hind limb suspension would reduce atrophy. Mice were suspended 18 days, with or without daily ISDN (66mg/kg). Muscles were examined for atrophy (weight, fiber diameter); regulatory changes in atrogin-1 (a negative regulator of muscle mass), myostatin (inhibit myogenesis), and satellite cell proliferation; and metabolic responses in myosin heavy chains (MyHCs), liver lipid, and hypothalamic gene expression...
December 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29276516/myostatin-promotes-interleukin-1%C3%AE-expression-in-rheumatoid-arthritis-synovial-fibroblasts-through-inhibition-of-mir-21-5p
#9
Sung-Lin Hu, An-Chen Chang, Chien-Chung Huang, Chun-Hao Tsai, Cheng-Chieh Lin, Chih-Hsin Tang
Rheumatoid arthritis (RA) is characterized by the infiltration of a number of pro-inflammatory cytokines into synovial fluid and patients with RA often develop joint destruction and deficits in muscle mass. The growth factor myostatin is a key regulator linking muscle mass and bone structure. We sought to determine whether myostatin regulates rheumatoid synovial fibroblast activity and inflammation in RA. We found that levels of myostatin and interleukin (IL)-1β (a key pro-inflammatory cytokine in RA) in synovial fluid from RA patients were overexpressed and positively correlated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29247983/relative-abundance-of-mature-myostatin-rather-than-total-myostatin-is-negatively-associated-with-bone-mineral-density-in-chinese
#10
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
https://www.readbyqxmd.com/read/29246653/myostatin-and-adipokines-the-role-of-the-metabolically-unhealthy-obese-phenotype-in-muscle-function-and-aerobic-capacity-in-young-adults
#11
Lívia Pinheiro Carvalho, Renata Pedrolongo Basso-Vanelli, Luciana Di Thommazo-Luporini, Renata Gonçalves Mendes, Manoel Carneiro Oliveira-Junior, Rodolfo de Paula Vieira, José Carlos Bonjorno-Junior, Cláudio Ricardo Oliveira, Rafael Luporini, Audrey Borghi-Silva
Obesity is often associated with metabolic disorders. However, some obese people can present a metabolically healthy phenotype, despite having excessive body fat. Obesity-related cytokines, such as myostatin (MSTN), leptin (LP) and adiponectin (ADP) appear to be key factors for the regulation of muscle and energy metabolism. Our aim was to compare lipid, glucose-insulin and inflammatory (tumor necrosis factor alpha; TNF-α) profiles, muscle function, energy expenditure and aerobic capacity between healthy normal-weight (NW) adults, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) adults; to study the associations between these outcomes and the cytokines MSTN, ADP, LP; and to establish cutoffs for MSTN and LP/ADP to identify the MUHO phenotype...
December 12, 2017: Cytokine
https://www.readbyqxmd.com/read/29242963/effect-of-strontium-ranelate-on-the-muscle-and-vertebrae-of-ovariectomized-rats
#12
D Saul, B Harlas, A Ahrabi, R L Kosinsky, D B Hoffmann, M Wassmann, R Wigger, K O Böker, S Sehmisch, M Komrakova
Osteoporosis is often accompanied by sarcopenia. The effect of strontium ranelate (SR) on muscle tissue has not been investigated sufficiently. In this study, the effect of different SR treatments on muscle was studied. Additionally, the lumbar vertebrae were analyzed. Three-month-old female rats were divided into five groups (n = 12): Group 1: untreated (NON-OVX); Group 2: ovariectomized and left untreated (OVX); Group 3: SR after OVX until the study ended (13 weeks, SR prophylaxis and therapy = pr+th); Group 4: OVX and SR for 8 weeks (SR prophylaxis = pr); Group 5: SR for 5 weeks from the 8 week after OVX (SR therapy = SR th)...
December 14, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29234200/nutrition-and-muscle-in-cirrhosis
#13
REVIEW
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
https://www.readbyqxmd.com/read/29230965/prevention-of-chemotherapy-induced-cachexia-by-acvr2b-ligand-blocking-has-different-effects-on-heart-and-skeletal-muscle
#14
Juha J Hulmi, Tuuli A Nissinen, Markus Räsänen, Joni Degerman, Juulia H Lautaoja, Karthik Amudhala Hemanthakumar, Janne T Backman, Olli Ritvos, Mika Silvennoinen, Riikka Kivelä
BACKGROUND: Toxicity of chemotherapy on skeletal muscles and the heart may significantly contribute to cancer cachexia, mortality, and decreased quality of life. Doxorubicin (DOX) is an effective cytostatic agent, which unfortunately has toxic effects on many healthy tissues. Blocking of activin receptor type IIB (ACVR2B) ligands is an often used strategy to prevent skeletal muscle loss, but its effects on the heart are relatively unknown. METHODS: The effects of DOX treatment with or without pre-treatment with soluble ACVR2B-Fc (sACVR2B-Fc) were investigated...
December 11, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29230835/genetic-contributions-to-precocity-traits-in-racing-thoroughbreds
#15
G Farries, P A McGettigan, K F Gough, B A McGivney, D E MacHugh, L M Katz, E W Hill
Adaptation to early training and racing (i.e. precocity), which is highly variable in racing Thoroughbreds, has implications for the selection and training of horses. We hypothesised that precocity in Thoroughbred racehorses is heritable. Age at first sprint training session (work day), age at first race and age at best race were used as phenotypes to quantify precocity. Using high-density SNP array data, additive SNP heritability (hSNP2) was estimated to be 0.17, 0.14 and 0.17 for the three traits respectively...
December 12, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29228005/rna-seq-reveals-transcriptome-changes-in-goats-following-myostatin-gene-knockout
#16
Lamei Wang, Bei Cai, Shiwei Zhou, Haijing Zhu, Lei Qu, Xiaolong Wang, Yulin Chen
Myostatin (MSTN) is a powerful negative regulator of skeletal muscle mass in mammalian species that is primarily expressed in skeletal muscles, and mutations of its encoding gene can result in the double-muscling trait. In this study, the CRISPR/Cas9 technique was used to edit MSTN in Shaanbei Cashmere goats and generate knockout animals. RNA sequencing was used to determine and compare the transcriptome profiles of the muscles from three wild-type (WT) goats, three fibroblast growth factor 5 (FGF5) knockout goats (FGF5+/- group) and three goats with disrupted expression of both the FGF5 and MSTN genes (FM+/- group)...
2017: PloS One
https://www.readbyqxmd.com/read/29226558/detection-of-the-human-anti-actrii-antibody-bimagrumab-in-serum-by-means-of-affinity-purification-tryptic-digestion-and-lc-hrms
#17
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
https://www.readbyqxmd.com/read/29224025/alterations-in-adiposity-and-glucose-homeostasis-in-adult-gasp-1-overexpressing-mice
#18
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...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29216301/chronic-dietary-supplementation-with-soy-protein-improves-muscle-function-in-rats
#19
Ramzi J Khairallah, Karen M O'Shea, Christopher W Ward, Dustie N Butteiger, Ratna Mukherjea, Elaine S Krul
Athletes as well as elderly or hospitalized patients use dietary protein supplementation to maintain or grow skeletal muscle. It is recognized that high quality protein is needed for muscle accretion, and can be obtained from both animal and plant-based sources. There is interest to understand whether these sources differ in their ability to maintain or stimulate muscle growth and function. In this study, baseline muscle performance was assessed in 50 adult Sprague-Dawley rats after which they were assigned to one of five semi-purified "Western" diets (n = 10/group) differing only in protein source, namely 19 kcal% protein from either milk protein isolate (MPI), whey protein isolate (WPI), soy protein isolate (SPI), soy protein concentrate (SPC) or enzyme-treated soy protein (SPE)...
2017: PloS One
https://www.readbyqxmd.com/read/29212003/soce-is-important-for-maintaining-sarcoplasmic-calcium-content-and-release-in-skeletal-muscle-fibers
#20
Mónika Sztretye, Nikolett Geyer, János Vincze, Dána Al-Gaadi, Tamás Oláh, Péter Szentesi, Gréta Kis, Miklós Antal, Ildikó Balatoni, László Csernoch, Beatrix Dienes
Store-operated Ca2+ entry (SOCE) is a Ca2+-entry process activated by the depletion of intracellular stores and has an important role in many cell types. In skeletal muscle, however, its role during physiological muscle activation has been controversial. To address this question, sarcoplasmic reticulum (SR) calcium release in a mouse strain with a naturally occurring mutation in the myostatin gene (Compact (Cmpt)) leading to a hypermuscular yet reduced muscle-force phenotype was compared to that in wild-type mice...
December 5, 2017: Biophysical Journal
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