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https://www.readbyqxmd.com/read/28218617/chimeric-protein-repair-of-laminin-polymerization-ameliorates-muscular-dystrophy-phenotype
#1
Karen K McKee, Stephanie C Crosson, Sarina Meinen, Judith R Reinhard, Markus A Rüegg, Peter D Yurchenco
Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation in Lama2 (dy2J mice) express a nonpolymerizing form of laminin-211 (Lm211) and are a model for ambulatory-type Lmα2-deficient muscular dystrophy. Here, we developed transgenic dy2J mice with muscle-specific expression of αLNNd, a laminin/nidogen chimeric protein that provides a missing polymerization domain. Muscle-specific expression of αLNNd in dy2J mice resulted in strong amelioration of the dystrophic phenotype, manifested by the prevention of fibrosis and restoration of forelimb grip strength...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28215905/apobec2-negatively-regulates-myoblast-differentiation-in-muscle-regeneration
#2
Hideaki Ohtsubo, Yusuke Sato, Takahiro Suzuki, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi
Recently we found that the deficiency of APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, leads to a diminished muscle mass and increased myofiber with centrally-located nuclei known as dystrophic phenotypes. APOBEC2 expression is predominant in skeletal and cardiac muscles and elevated exclusively at the early-differentiation phase of wild-type (WT) myoblast cultures; however the physiological significance is still un-known. Here we show that APOBEC2 is a key negative regulator of myoblast differentiation in muscle regeneration...
February 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28211476/novel-roles-for-staufen1-in-embryonal-and-alveolar-rhabdomyosarcoma-via-c-myc-dependent-and-independent-events
#3
Tara E Crawford Parks, Kristen A Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N Cowan, Jocelyn Côté, Bernard J Jasmin
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208626/2-o-methyl-rna-ethylene-bridged-nucleic-acid-chimera-antisense-oligonucleotides-to-induce-dystrophin-exon-45-skipping
#4
REVIEW
Tomoko Lee, Hiroyuki Awano, Mariko Yagi, Masaaki Matsumoto, Nobuaki Watanabe, Ryoya Goda, Makoto Koizumi, Yasuhiro Takeshima, Masafumi Matsuo
Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28207742/narciclasine-attenuates-diet-induced-obesity-by-promoting-oxidative-metabolism-in-skeletal-muscle
#5
Sofi G Julien, Sun-Yee Kim, Reinhard Brunmeir, Joanna R Sinnakannu, Xiaojia Ge, Hongyu Li, Wei Ma, Jadegoud Yaligar, Bhanu Prakash Kn, Sendhil S Velan, Pia V Röder, Qiongyi Zhang, Choon Kiat Sim, Jingyi Wu, Marta Garcia-Miralles, Mahmoud A Pouladi, Wei Xie, Craig McFarlane, Weiping Han, Feng Xu
Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity...
February 2017: PLoS Biology
https://www.readbyqxmd.com/read/28196858/the-2016-walter-b-cannon-lecture-deconstructing-metabolic-inflammation-using-cellular-systems
#6
Kenny L Chan, Parastoo Boroumand, Marciane Milanski, Nicolas J Pillon, Philip J Bilan, Amira Klip
Over the past years we have embarked in a systematic analysis of the effect of obesity or fatty acids on circulating monocytes, microvascular endothelial cells, macrophages and skeletal muscle cells. Using cell culture strategies, we have deconstructed complex physiological systems, then reconstructed 'partial equations' to better understand cell-to-cell communication. Through these approaches we identified that in high saturated fat environments, cell-autonomous pro-inflammatory pathways are activated in monocytes and endothelial cells, promoting monocyte adhesion and transmigration...
February 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28188344/skeletal-muscle-secretome-in-duchenne-muscular-dystrophy-a-pivotal-anti-inflammatory-role-of-adiponectin
#7
S Lecompte, M Abou-Samra, R Boursereau, L Noel, S M Brichard
BACKGROUND: Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28188262/mapk-signaling-pathways-and-hdac3-activity-are-disrupted-during-emerin-null-myogenic-progenitor-differentiation
#8
Carol M Collins, Joseph Ellis, James M Holaska
Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). Emerin is an integral inner nuclear membrane protein and a component of the nuclear lamina. EDMD is characterized by skeletal muscle wasting, cardiac conduction defects and tendon contractures. The failure to regenerate skeletal muscle is predicted to contribute to the skeletal muscle pathology of EDMD. We hypothesize muscle regeneration defects are caused by impaired muscle stem cell differentiation. Myogenic progenitors derived from emerin-null mice were used to confirm their impaired differentiation and analyze selected myogenic molecular pathways...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28188178/activation-of-the-hypoxia-inducible-factor-1%C3%AE-promotes-myogenesis-through-the-noncanonical-wnt-pathway-leading-to-hypertrophic-myotubes
#9
Federica Cirillo, Giulia Resmini, Andrea Ghiroldi, Marco Piccoli, Sonia Bergante, Guido Tettamanti, Luigi Anastasia
Regeneration of skeletal muscle is a complex process that requires the activation of quiescent adult stem cells, called satellite cells, which are resident in hypoxic niches in the tissue. Hypoxia has been recognized as a key factor to maintain stem cells in an undifferentiated state. Herein we report that hypoxia plays a fundamental role also in activating myogenesis. In particular, we found that the activation of the hypoxia-inducible factor (HIF)-1α under hypoxia, in murine skeletal myoblasts, leads to activation of MyoD through the noncanonical Wnt/β-catenin pathway...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28186504/a-defective-dntp-pool-hinders-dna-replication-in-cell-cycle-reactivated-terminally-differentiated-muscle-cells
#10
Deborah Pajalunga, Elisa Franzolin, Martina Stevanoni, Sara Zribi, Nunzia Passaro, Aymone Gurtner, Samantha Donsante, Daniela Loffredo, Lidia Losanno, Vera Bianchi, Antonella Russo, Chiara Rampazzo, Marco Crescenzi
Terminally differentiated cells are defined by their inability to proliferate. When forced to re-enter the cell cycle, they generally cannot undergo long-term replication. Our previous work with myotubes has shown that these cells fail to proliferate because of their intrinsic inability to complete DNA replication. Moreover, we have reported pronounced modifications of deoxynucleotide metabolism during myogenesis. Here we investigate the causes of incomplete DNA duplication in cell cycle-reactivated myotubes (rMt)...
February 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28185894/trpc1-and-trpc4-channels-functionally-interact-with-stim1l-to-promote-myogenesis-and-maintain-fast-repetitive-ca-2-release-in-human-myotubes
#11
Fabrice Antigny, Jessica Sabourin, Sophie Saüc, Laurent Bernheim, Stéphane Koenig, Maud Frieden
STIM1 and Orai1 are essential players of store-operated Ca(2+) entry (SOCE) in human skeletal muscle cells and are required for adult muscle differentiation. Besides these two proteins, TRPC (transient receptor potential canonical) channels and STIM1L (a longer STIM1 isoform) are also present on muscle cells. In the present study, we assessed the role of TRPC1, TRPC4 and STIM1L in SOCE, in the maintenance of repetitive Ca(2+) transients and in muscle differentiation. Knockdown of TRPC1 and TRPC4 reduced SOCE by about 50% and significantly delayed the onset of Ca(2+) entry, both effects similar to STIM1L invalidation...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28183860/diminished-satellite-cell-fusion-and-s6k1-expression-in-myotubes-derived-from-skeletal-muscle-of-low-birth-weight-neonatal-pigs
#12
Ying Chen, Haibo Zhu, Sydney R McCauley, Lidan Zhao, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)-mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin-like growth factor (IGF)-I stimulation in SC-derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3-d-old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28179457/microtubule-motors-involved-in-nuclear-movement-during-skeletal-muscle-differentiation
#13
V Gache, E R Gomes, B Cadot
Nuclear positioning is a determining event in several cellular processes such as fertilization, cell migration and cell differentiation. The structure and function of muscle cells, which contain hundreds of nuclei, have been described to rely, in part, on proper nuclear positioning. Remarkably, in the course of muscle differentiation, nuclear movements along the myotube axis might represent the event required for the evenly positioning of nuclei in the mature myofiber. Here we report the analysis of nuclear behavior, time in motion, speed and alignment, during myotube differentiation and temporal interference of cytoskeletal microtubule related motors...
February 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28176826/annexin-a5-organized-in-2d-network-at-the-plasmalemma-eases-human-trophoblast-fusion
#14
Severine A Degrelle, Pascale Gerbaud, Ludovic Leconte, Fatima Ferreira, Guillaume Pidoux
Only a limited number of human cells can fuse to form a multinucleated syncytium. Cell fusion occurs as part of the differentiation of some cell types, including myotubes in muscle and osteoclasts in remodeling bone. In the differentiation of the human placenta, mononuclear cytotrophoblasts aggregate and fuse to form endocrinologically active, non-proliferative, multinucleated syncytia. These syncytia allow the exchange of nutrients and gases between the maternal and fetal circulation. Alteration of syncytial formation during pregnancy affects fetal growth and the outcome of the pregnancy...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174253/vitamin-d-induces-myogenic-differentiation-in-skeletal-muscle-derived-stem-cells
#15
Melissa Braga, Zena Simmons, Keith C Norris, Monica G Ferrini, Jorge N Artaza
Skeletal muscle wasting is a serious disorder associated with health conditions such as aging, chronic kidney disease, and AIDS. Vitamin D is most widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance. Recently, Vitamin D supplementation has been shown to improve muscle performance and reduce the risk of falls in Vitamin D deficient older adults. However, little is known of the underlying molecular mechanism(s) or the role it plays in myogenic differentiation...
February 7, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28174179/s100b-impairs-glycolysis-via-enhanced-poly-adp-ribosyl-ation-of-glyceraldehyde-3-phosphate-dehydrogenase-in-rodent-muscle-cells
#16
Kaori Hosokawa, Yoji Hamada, Atsushi Fujiya, Masatoshi Murase, Ryuya Maekawa, Yasuhiro Niwa, Takako Izumoto, Yusuke Seino, Shin Tsunekawa, Hiroshi Arima
S100 calcium-binding protein B (S100B), a multifunctional macromolecule mainly expressed in nerve tissues and adipocytes, has been suggested to contribute to the pathogenesis of obesity. To clarify the role of S100B in insulin action and glucose metabolism in peripheral tissues, we investigated the effect of S100B on glycolysis in myoblast and myotube cells. Rat myoblast L6 cells were treated with recombinant mouse S100B to examine glucose consumption, lactate production, glycogen accumulation, glycolytic metabolites and enzyme activity, insulin signaling, and poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)...
February 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28165492/enhanced-development-of-skeletal-myotubes-from-porcine-induced-pluripotent-stem-cells
#17
Nicholas J Genovese, Timothy L Domeier, Bhanu Prakash V L Telugu, R Michael Roberts
The pig is recognized as a valuable model in biomedical research in addition to its agricultural importance. Here we describe a means for generating skeletal muscle efficiently from porcine induced pluripotent stem cells (piPSC) in vitro thereby providing a versatile platform for applications ranging from regenerative biology to the ex vivo cultivation of meat. The GSK3B inhibitor, CHIR99021 was employed to suppress apoptosis, elicit WNT signaling events and drive naïve-type piPSC along the mesoderm lineage, and, in combination with the DNA methylation inhibitor 5-aza-cytidine, to activate an early skeletal muscle transcription program...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164151/graphene-foam-as-a-three-dimensional-platform-for-myotube-growth
#18
Eric Krueger, A Nicole Chang, Dale Brown, Josh Eixenberger, Raquel Brown, Sepideh Rastegar, Katie M Yocham, Kurtis D Cantley, David Estrada
This study demonstrates the growth and differentiation of C2C12 myoblasts into functional myotubes on 3-dimensional graphene foam bioscaffolds. Specifically, we establish both bare and laminin coated graphene foam as a biocompatible platform for muscle cells and identify that electrical coupling stimulates cell activity. Cell differentiation and functionality is determined by the expression of myotube heavy chain protein and Ca(2+) fluorescence, respectively. Further, our data show that the application of a pulsed electrical stimulus to the graphene foam initiates myotube contraction and subsequent localized substrate movement of over 100 micrometers...
August 8, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28163294/metabolic-suppression-by-3-iodothyronamine-induced-muscle-cell-atrophy-via-activation-of-foxo-proteasome-signaling-and-downregulation-of-akt1-s6k-signaling
#19
Hyunwoo Ju, Taewan Kim, Chan-Moon Chung, Junsoo Park, Takeshi Nikawa, Kyoungsook Park, Inho Choi
The homeostasis of muscle properties depends on both physical and metabolic stresses. Whereas physical stress entails metabolic response for muscle homeostasis, the latter does not necessarily involve the former and may thus solely affect the homeostasis. We here report that metabolic suppression by the hypometabolic agent 3-iodothyronamine (T1AM) induced muscle cell atrophy without physical stress. We observed that the oxygen consumption rate of C2C12 myotubes decreased 40% upon treatment with 75 μM T1AM for 6 h versus 10% in the vehicle (dimethyl sulfoxide) control...
February 3, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28161635/effect-of-tcea3-on-the-differentiation-of-bovine-skeletal-muscle-satellite-cells
#20
Yue Zhu, Hui-Li Tong, Shu-Feng Li, Yun-Qin Yan
Bovine muscle-derived satellite cells (MDSCs) are important for animal growth. In this study, the effect of transcription elongation factor A3 (TCEA3) on bovine MDSC differentiation was investigated. Western blotting, immunofluorescence assays, and cytoplasmic and nuclear protein isolation and purification techniques were used to determine the expression pattern and protein localization of TCEA3 in bovine MDSCs during in vitro differentiation. TCEA3 expression was upregulated using the CRISPR/Cas9 technique to study its effects on MDSC differentiation in vitro...
February 2, 2017: Biochemical and Biophysical Research Communications
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