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https://www.readbyqxmd.com/read/28303574/functional-impact-of-an-oculopharyngeal-muscular-dystrophy-mutation-in-pabpn1
#1
Maricela García-Castañeda, Ana Victoria Vega, Rocío Rodríguez, Maria Guadalupe Montiel-Jaen, Bulmaro Cisneros, Angel Zarain-Herzberg, Guillermo Avila
Oculopharyngeal muscular dystrophy (OPMD) is linked to mutations in the gene encoding poly(A)-binding protein nuclear 1 (PABPN1). OPMD mutations consist in an expansion of a tract that contains 10 alanines (to 12-17). The disease courses with muscle weakness that begins in adulthood, but the underlying mechanism is unclear. Here we investigated functional effects of PABPN1 and an OPMD mutation (PABPN1-17A), using myotubes transfected with cDNAs encoding these proteins (GFP-tagged). PABPN1 stimulated myoblast fusion (100%), but PABPN1-17A failed to mimic this effect...
March 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28300015/frzb-and-melusin-overexpressed-in-lgmd2a-regulate-integrin-%C3%AE-1d-isoform-replacement-altering-myoblast-fusion-and-the-integrin-signalling-pathway
#2
Oihane Jaka, Leire Casas-Fraile, Margarita Azpitarte, Ana Aiastui, Adolfo López de Munain, Amets Sáenz
Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene. However, the underlying pathophysiological mechanisms of muscle degeneration are still not well understood. The objective of this study was to assess the relevance of genes with differential expression in the muscle of LGMD2A patients. For this purpose, we analysed their in vitro expression in primary cultures of human myoblasts and myotubes...
March 16, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28258011/mir-16-controls-myoblast-proliferation-and-apoptosis-through-directly-suppressing-bcl2-and-foxo1-activities
#3
Xinzheng Jia, Hongjia Ouyang, Bahareldin Ali Abdalla, Haiping Xu, Qinghua Nie, Xiquan Zhang
Myogenesis mainly involves several steps including myoblast proliferation, differentiation, apoptosis and fusion. Except for muscle specific regulators, few miRNAs were proved to coordinate this complex process. Here, we reported that miR-16 inhibited myoblast proliferation and promoted myoblast apoptosis by directly targeting Bcl2 and FOXO1. The expression level of miR-16 was significantly decreased in the hypertrophic pectoral muscle compared to the normal pectoral muscle in chicken. In vitro, elevating miR-16 significantly inhibited myoblast proliferation and promoted myoblast apoptosis, resulting in about 11...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28249984/adult-muscle-formation-requires-drosophila-moleskin-for-proliferation-of-wing-disc-associated-muscle-precursors
#4
Kumar Vishal, David S Brooks, Simranjot Bawa, Samantha Gameros, Marta Stetsiv, Erika R Geisbrecht
Adult muscle precursor (AMP) cells located in the notum of the larval wing disc undergo rapid amplification and eventual fusion to generate the Drosophila melanogaster indirect flight muscles (IFMs). Here we find that loss of Moleskin (Msk) function in these wing disc-associated myoblasts reduces the overall AMP pool size, resulting in the absence of IFM formation. This myoblast loss is due to a decrease in the AMP proliferative capacity and is independent of cell death. In contrast, disruption of Msk during pupal myoblast proliferation does not alter the AMP number, suggesting that Msk is specifically required for larval AMP proliferation...
March 1, 2017: Genetics
https://www.readbyqxmd.com/read/28235489/resveratrol-stimulates-mitochondrial-fusion-by-a-mechanism-requiring-mitofusin-2
#5
Ellen L Robb, Fereshteh Moradi, Lucas A Maddalena, Andrew J F Valente, Joao Fonseca, Jeffrey A Stuart
Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28224701/pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies-in-necrotizing-myopathies-myofiber-atrophy-and-impairment-of-muscle-regeneration-in-necrotizing-autoimmune-myopathies
#6
Louiza Arouche-Delaperche, Yves Allenbach, Damien Amelin, Corinna Preusse, Vincent Mouly, Wladimir Mauhin, Gaelle Dzangue Tchoupou, Laurent Drouot, Olivier Boyer, Werner Stenzel, Gillian Butler-Browne, Olivier Benveniste
OBJECTIVE: Immune mediated necrotizing myopathies (IMNM) may be associated with either anti-SRP or anti-HMGCR antibodies (Abs) and the titer of these Abs is correlated with the disease activity. We investigated if anti-SRP and anti-HMGCR Abs could be involved in muscle damages. METHODS: Muscle biopsies of patients were analyzed for atrophy and regeneration, by measuring the fibers size and by performing immunostaining of neonatal myosin heavy chain. To further understand the role of the Abs in the pathology, we performed muscle cell co-culture with the Abs...
February 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28215905/apobec2-negatively-regulates-myoblast-differentiation-in-muscle-regeneration
#7
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/28188264/immortalized-human-myotonic-dystrophy-muscle-cell-lines-to-assess-therapeutic-compounds
#8
Arandel Ludovic, Polay-Espinosa Micaela, Matloka Magdalena, Bazinet Audrey, De Dea Diniz Damily, Naouar Naïra, Rau Frédérique, Jollet Arnaud, Edom-Vovard Frédérique, Mamchaoui Kamel, Tarnopolsky Mark, Puymirat Jack, Battail Christophe, Boland Anne, Deleuze Jean-Francois, Mouly Vincent, Klein F Arnaud, Furling Denis
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA-aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared to control and DM2 cells...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28186492/requirement-of-myomaker-mediated-stem-cell-fusion-for-skeletal-muscle-hypertrophy
#9
Qingnian Goh, Douglas P Millay
Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28168016/deletion-of-the-ste20-like-kinase-slk-in-skeletal-muscle-results-in-a-progressive-myopathy-and-muscle-weakness
#10
Benjamin R Pryce, Khalid N Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw, Luc A Sabourin
BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28154884/antibody-mediated-enzyme-replacement-therapy-targeting-both-lysosomal-and-cytoplasmic-glycogen-in-pompe-disease
#11
Haiqing Yi, Tao Sun, Dustin Armstrong, Scott Borneman, Chunyu Yang, Stephanie Austin, Priya S Kishnani, Baodong Sun
Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease...
February 2, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28153048/deletion-of-the-ste20-like-kinase-slk-in-skeletal-muscle-results-in-a-progressive-myopathy-and-muscle-weakness
#12
Benjamin R Pryce, Khalid N Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw, Luc A Sabourin
BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle...
February 2, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28138962/pax3-foxo1-is-essential-for-tumour-initiation-and-maintenance-but-not-recurrence-in-a-human-myoblast-model-of-rhabdomyosarcoma
#13
Puspa R Pandey, Bishwanath Chatterjee, Mary E Olanich, Javed Khan, Markku M Miettinen, Stephen M Hewitt, Frederic G Barr
The PAX3-FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline-inducible PAX3-FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3-FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3-FOXO1 and MYCN expression resulted in transformation...
April 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28101909/efficient-transdifferentiation-of-human-dermal-fibroblasts-into-skeletal-muscle
#14
Selwa Mokhtar Boularaoui, Khaled M A Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E Kondash, George A Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou
Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused due to severe injury, congenital defects, or tumor ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097017/study-of-myoblast-differentiation-using-multi-dimensional-scaffolds-consisting-of-nano-and-micropatterns
#15
Sung Ho Cha, Hyun Jong Lee, Won-Gun Koh
BACKGROUND: The topographical cue is major influence on skeletal muscle cell culture because the structure is highly organized and consists of long parallel bundles of multinucleated myotubes that are formed by differentiation and fusion of myoblast satellite cells. In this technical report, we fabricated a multiscale scaffold using electrospinning and poly (ethylene glycol) (PEG) hydrogel micropatterns to monitor the cell behaviors on nano- and micro-alignment combined scaffolds with different combinations of angles...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28062562/keep-your-friends-close-cell-cell-contact-and-skeletal-myogenesis
#16
Robert S Krauss, Giselle A Joseph, Aviva J Goel
Development of skeletal muscle is a multistage process that includes lineage commitment of multipotent progenitor cells, differentiation and fusion of myoblasts into multinucleated myofibers, and maturation of myofibers into distinct types. Lineage-specific transcriptional regulation lies at the core of this process, but myogenesis is also regulated by extracellular cues. Some of these cues are initiated by direct cell-cell contact between muscle precursor cells themselves or between muscle precursors and cells of other lineages...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28044437/body-mass-index-change-in-gastrointestinal-cancer-and-chronic-obstructive-pulmonary-disease-is-associated-with-dedicator-of-cytokinesis-1
#17
Merry-Lynn Noelle McDonald, Sungho Won, Manuel Mattheisen, Peter J Castaldi, Michael H Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I Rennard, David A Lomas, Emiel F M Wouters, Alvar Agusti, Richard Casaburi, Christoph P Lange, George O'Connor, Craig P Hersh, Edwin K Silverman
BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162)...
January 2, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27965114/myogenic-differentiation-depends-on-the-interplay-of-grb2-and-n-wasp
#18
Payal Mitra, Thirumaran Thanabalu
Myogenesis requires a well-coordinated withdrawal from cell cycle, morphological changes and cell fusion mediated by actin cytoskeleton. Grb2 is an adaptor protein whose central SH2 domain binds to phosphorylated tyrosine residues of activated receptors and activates intracellular signaling pathway, while its N-terminal and C-terminal SH3 domains bind to proline rich proteins such as N-WASP (Neural-Wiskott Aldrich Syndrome Protein). We found that the expression of Grb2 was increased at the beginning of differentiation and remained constant during differentiation in C2C12 myoblasts...
December 10, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27964750/laminin-521-maintains-differentiation-potential-of-mouse-and-human-satellite-cell-derived-myoblasts-during-long-term-culture-expansion
#19
Christopher M Penton, Vasudeo Badarinarayana, Joy Prisco, Elaine Powers, Mark Pincus, Ronald E Allen, Paul R August
BACKGROUND: Large-scale expansion of myogenic progenitors is necessary to support the development of high-throughput cellular assays in vitro and to advance genetic engineering approaches necessary to develop cellular therapies for rare muscle diseases. However, optimization has not been performed in order to maintain the differentiation capacity of myogenic cells undergoing long-term cell culture. Multiple extracellular matrices have been utilized for myogenic cell studies, but it remains unclear how different matrices influence long-term myogenic activity in culture...
December 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27938324/analysis-and-quantification-of-in-vitro-myoblast-fusion-using-the-ladd-multiple-stain
#20
Rhys McColl, Mthokozisi Nkosi, Celia Snyman, Carola Niesler
Myoblast fusion, which is essential for muscle development, regeneration, and repair, can be assessed in vitro via the calculation of a fusion index. Traditionally, this requires use of either immunocytochemistry or fluorescently-labeled cytoskeletal staining, followed by microscopy and laborious analysis. The expense and time-consuming nature of the optimization and application of antibody-based techniques such as immunocytochemistry, as well as the need for specialized analytical equipment such as fluorescence microscopes, presents a barrier to the routine analysis of this crucial step during terminal differentiation...
December 1, 2016: BioTechniques
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