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https://www.readbyqxmd.com/read/28608457/potential-therapeutic-interventions-for-chronic-kidney-disease-associated-sarcopenia-via-indoxyl-sulfate-induced-mitochondrial-dysfunction
#1
Yuki Enoki, Hiroshi Watanabe, Riho Arake, Rui Fujimura, Kana Ishiodori, Tadashi Imafuku, Kento Nishida, Ryusei Sugimoto, Saori Nagao, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
BACKGROUND: Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice...
June 12, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28607086/specific-targeting-of-tgf-%C3%AE-family-ligands-demonstrates-distinct-roles-in-the-regulation-of-muscle-mass-in-health-and-disease
#2
Justin L Chen, Kelly L Walton, Adam Hagg, Timothy D Colgan, Katharine Johnson, Hongwei Qian, Paul Gregorevic, Craig A Harrison
The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28539643/myostatin-a-profibrotic-factor-and-the-main-inhibitor-of-striated-muscle-mass-is-present-in-the-penile-and-vascular-smooth-muscle
#3
I Kovanecz, M Masouminia, R Gelfand, D Vernet, J Rajfer, N F Gonzalez-Cadavid
Myostatin is present in striated myofibers but, except for myometrial cells, has not been reported within smooth muscle cells (SMC). We investigated in the rat whether myostatin is present in SMC within the penis and the vascular wall and, if so, whether it is transcriptionally expressed and associated with the loss of corporal SMC occurring in certain forms of erectile dysfunction (ED). Myostatin protein was detected by immunohistochemistry/fluorescence and western blots in the perineal striated muscles, and also in the SMC of the penile corpora, arteries and veins, and aorta...
May 25, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28533206/myostatin-like-proteins-regulate-synaptic-function-and-neuronal-morphology
#4
Hrvoje Augustin, Kieran McGourty, Joern R Steinert, Helena M Cochemé, Jennifer Adcott, Melissa Cabecinha, Alec Vincent, Els F Halff, Josef T Kittler, Emmanuel Boucrot, Linda Partridge
Growth factors of the TGF-β superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of both Myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of Myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner...
May 22, 2017: Development
https://www.readbyqxmd.com/read/28471505/role-of-follistatin-in-muscle-and-bone-alterations-induced-by-gravity-change-in-mice
#5
Naoyuki Kawao, Hironobu Morita, Koji Obata, Kohei Tatsumi, Hiroshi Kaji
Interactions between muscle and bone have been recently noted. We reported that the vestibular system plays crucial roles in the changes in muscle and bone induced by hypergravity in mice. However, the details of the mechanisms by which gravity change affects muscle and bone through the vestibular system still remain unknown. Here, we investigated the roles of humoral factors linking muscle to bone and myostatin-related factors in the hypergravity-induced changes in muscle and bone in mice with vestibular lesions (VL)...
May 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28406165/myostatin-mediates-abdominal-aortic-atherosclerosis-progression-by-inducing-vascular-smooth-muscle-cell-dysfunction-and-monocyte-recruitment
#6
D Verzola, S Milanesi, M Bertolotto, S Garibaldi, B Villaggio, C Brunelli, M Balbi, P Ameri, F Montecucco, D Palombo, G Ghigliotti, G Garibotto, J H Lindeman, C Barisione
Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396837/myostatin-promotes-tenogenic-differentiation-of-c2c12-myoblast-cells-through-smad3
#7
Kazutaka Uemura, Masanori Hayashi, Toshiro Itsubo, Ayumu Oishi, Hiroko Iwakawa, Masatoshi Komatsu, Shigeharu Uchiyama, Hiroyuki Kato
Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in developing and adult skeletal muscle and negatively regulates skeletal muscle growth. Recently, myostatin has been found to be expressed in tendons and increases tendon fibroblast proliferation and the expression of tenocyte markers. C2C12 is a mouse myoblast cell line, which has the ability to transdifferentiate into osteoblast and adipocyte lineages. We hypothesized that myostatin is capable of inducing tenogenic differentiation of C2C12 cells...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28277951/within-winter-flexibility-in-muscle-masses-myostatin-and-cellular-aerobic-metabolic-intensity-in-passerine-birds
#8
David L Swanson, Marisa O King, William Culver, Yufeng Zhang
Metabolic rates of passerine birds are flexible traits that vary both seasonally and among and within winters. Seasonal variation in summit metabolic rates (Msum = maximum thermoregulatory metabolism) in birds is consistently correlated with changes in pectoralis muscle and heart masses and sometimes with variation in cellular aerobic metabolic intensity, so these traits might also be associated with shorter-term, within-winter variation in metabolic rates. To determine whether these mechanisms are associated with within-winter variation in Msum, we examined the effects of short-term (ST; 0-7 d), medium-term (MT; 14-30 d), and long-term (LT; 30-yr means) temperature variables on pectoralis muscle and heart masses, pectoralis expression of the muscle-growth inhibitor myostatin and its metalloproteinase activators TLL-1 and TLL-2, and pectoralis and heart citrate synthase (CS; an indicator of cellular aerobic metabolic intensity) activities for two temperate-zone resident passerines, house sparrows (Passer domesticus) and dark-eyed juncos (Junco hyemalis)...
March 2017: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/28247316/selecting-potential-pharmacological-interventions-in-sarcopenia
#9
Amanda J Kilsby, Avan A Sayer, Miles D Witham
Sarcopenia of age is prevalent and costly and proven pharmacological interventions are currently lacking. The pathophysiology of sarcopenia is incompletely understood but appears to involve multiple pathways, including inflammation, hormonal dysregulation, impaired regeneration, mitochondrial dysfunction and denervation. There are several ways in which we might select potential pharmacological interventions for testing in clinical trials. These include a 'bottom-up' approach using basic science to elucidate the molecular processes involved and identify potential targets from this knowledge-a strategy that has led to the development of myostatin inhibitors...
April 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28217409/muscle-derived-stem-cells-stimulate-muscle-myofiber-repair-and-counteract-fat-infiltration-in-a-diabetic-mouse-model-of-critical-limb-ischemia
#10
J Tsao, I Kovanecz, N Awadalla, R Gelfand, I Sinha-Hikim, R A White, N F Gonzalez-Cadavid
BACKGROUND: Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D...
December 2016: Journal of Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28122601/inhibition-of-stat3-signaling-ameliorates-atrophy-of-the-soleus-muscles-in-mice-lacking-the-vitamin-d-receptor
#11
Suchitra D Gopinath
BACKGROUND: Although skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D signaling are less clear. To determine the molecular consequences of vitamin D signaling, we analyzed the role of signal transducer and activator of transcription 3 (Stat3) signaling, a known contributor to various muscle wasting pathologies, in skeletal muscles. METHODS: We isolated soleus (slow) and tibialis anterior (fast) muscles from mice lacking the vitamin D receptor (VDR(-/-)) and used western blot analysis, quantitative RTPCR, and pharmacological intervention to analyze muscle atrophy in VDR(-/-) mice...
January 25, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28105285/structural-basis-for-the-effective-myostatin-inhibition-of-the-mouse-myostatin-prodomain-derived-minimum-peptide
#12
Tomo Asari, Kentaro Takayama, Akari Nakamura, Takahiro Shimada, Akihiro Taguchi, Yoshio Hayashi
Myostatin inhibition is one of the promising strategies for treating muscle atrophic disorders, including muscular dystrophy. It is well-known that the myostatin prodomain derived from the myostatin precursor acts as an inhibitor of mature myostatin. In our previous study, myostatin inhibitory minimum peptide 1 (WRQNTRYSRIEAIKIQILSKLRL-amide) was discovered from the mouse myostatin prodomain. In the present study, alanine scanning of 1 demonstrated that the key amino acid residues for the effective inhibitory activity are rodent-specific Tyr and C-terminal aliphatic residues, in addition to N-terminal Trp residue...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28012893/matrix-gla-protein-an-extracellular-matrix-protein-regulates-myostatin-expression-in-the-muscle-developmental-program
#13
Sarafraz Ahmad, Arif Tasleem Jan, Mohammad Hassan Baig, Eun Ju Lee, Inho Choi
AIM: Skeletal muscle development involves interactions between intracellular and extracellular factors that act in concert to regulate the myogenic process. Matrix gla protein (MGP), a well-known inhibitor of calcification in soft tissues, has been reported to be highly up-regulated during myogenesis. Our interest in the regulation of muscle satellite cells (MSCs) by extracellular matrix (ECM) led us to investigate the effects of MGP during the progression of myogenesis. METHODOLOGY: Participation of MGP in the myogenic process was investigated in vitro using C2C12 cells, and knockdown of its gene was performed to determine its effects on the expression of myogenic regulatory factors (MRFs) and other ECM genes...
March 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27906072/actrii-blockade-protects-mice-from-cancer-cachexia-and-prolongs-survival-in-the-presence-of-anti-cancer-treatments
#14
Shinji Hatakeyama, Serge Summermatter, Marie Jourdain, Stefan Melly, Giulia C Minetti, Estelle Lach-Trifilieff
BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. METHODS: In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model...
July 26, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906065/dystrophin-deficient-dogs-with-reduced-myostatin-have-unequal-muscle-growth-and-greater-joint-contractures
#15
Joe N Kornegay, Daniel J Bogan, Janet R Bogan, Jennifer L Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C Warsing, Robert W Grange, Mihye Ahn, Cynthia J Balog-Alvarez, Steven W Cotten, Monte S Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra, Carl A Morris, Martin A Styner, Kathryn R Wagner
BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition...
April 4, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27897407/activin-a-induces-skeletal-muscle-catabolism-via-p38%C3%AE-mitogen-activated-protein-kinase
#16
Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li
BACKGROUND: Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined. METHODS: We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically...
April 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27695802/invited-review-inhibitors-of-myostatin-as-methods-of-enhancing-muscle-growth-and-development
#17
REVIEW
P R Chen, K Lee
With the increasing demand for affordable, high-quality meat, livestock and poultry producers must continually find ways to maximize muscle growth in their animals without compromising palatability of the meat products. Muscle mass relies on myoblast proliferation during prenatal or prehatch stages and fiber hypertrophy through protein synthesis and nuclei donation by satellite cells after birth or hatch. Therefore, understanding the cellular and molecular mechanisms of myogenesis and muscle development is of great interest...
August 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27690014/new-treatment-strategies-for-alcohol-induced-heart-damage
#18
REVIEW
Joaquim Fernández-Solà, Ana Planavila Porta
High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis...
September 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27628627/matrix-metalloproteinase-responsive-delivery-of-myostatin-inhibitors
#19
Alexandra C Braun, Marcus Gutmann, Regina Ebert, Franz Jakob, Henning Gieseler, Tessa Lühmann, Lorenz Meinel
PURPOSE: The inhibition of myostatin - a member of the transforming growth factor (TGF-β) family - drives regeneration of functional skeletal muscle tissue. We developed a bioresponsive drug delivery system (DDS) linking release of a myostatin inhibitor (MI) to inflammatory flares of myositis to provide self-regulated MI concentration gradients within tissues of need. METHODS: A protease cleavable linker (PCL) - responding to MMP upregulation - is attached to the MI and site-specifically immobilized on microparticle surfaces...
January 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/27605943/sarcopenia-in-heart-failure-mechanisms-and-therapeutic-strategies
#20
REVIEW
Agnese Collamati, Emanuele Marzetti, Riccardo Calvani, Matteo Tosato, Emanuela D'Angelo, Alex N Sisto, Francesco Landi
Chronic heart failure (CHF) is a highly prevalent condition among the elderly and is associated with considerable morbidity, institutionalization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments...
July 2016: Journal of Geriatric Cardiology: JGC
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