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https://www.readbyqxmd.com/read/28931313/muscle-expression-of-sod1g93a-triggers-the-dismantlement-of-neuromuscular-junction-via-pkc-theta
#1
Gabriella Dobrowolny, Martina Martini, Bianca Maria Scicchitano, Vanina Romanello, Simona Boncompagni, Carmine Nicoletti, Laura Pietrangelo, Simone De Panfilis, Angela Catizone, Marina Bouche, Marco Sandri, Rudiger Rudolf, Feliciano Protasi, Antonio Musaro
Aim Neuromuscular junction (NMJ) represents the morpho-functional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and Amyotrophic Lateral Sclerosis (ALS), display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Results Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1G93A in transgenic MLC/SOD1G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of Acetylcholine Receptor (AChR), and NMJ dismantlement...
September 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#2
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28915063/twist1-in-hypoxia-induced-pulmonary-hypertension-through-tgf%C3%AE-smad-signaling
#3
Tadanori Mammoto, Megan Muyleart, G Ganesh Konduri, Akiko Mammoto
Pulmonary hypertension (PH) is a devastating pulmonary vascular disease characterized by aberrant muscularization of the normally non-muscularized distal pulmonary arterioles. The expression of the transcription factor, Twist1, increases in the lungs of pulmonary arterial hypertension patients. However, the mechanisms by which Twist1 controls the pathogenesis of PH remain unclear. It is becoming clear that endothelial-to-mesenchymal transition (EndMT) contributes to various vascular pathologies including PH; Twist1 is known to mediate EndMT...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28910144/ask1-inhibition-halts-disease-progression-in-preclinical-models-of-pulmonary-arterial-hypertension
#4
Grant R Budas, Mario Boehm, Baktybek Kojonazarov, Gayathri Viswanathan, Xia Tian, Swathi Veeroju, Tatyana Novoyatleva, Friedrich Grimminger, Ford Hinojosa-Kirschenbaum, Hossein A Ghofrani, Norbert Weissmann, Werner Seeger, John T Liles, Ralph T Schermuly
RATIONALE Progression of pulmonary arterial hypertension (PAH) is associated with pathologic remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of mitogenactivated protein kinases (MAPKs) which stimulate apoptosis, inflammation and fibrosis. OBJECTIVES We investigated whether pharmacological inhibition of the redoxsensitive apical MAPK Apoptosis Signal-Regulating Kinase 1 (ASK1) can halt the progression of pulmonary vascular and RV remodeling...
September 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28899790/alisporivir-rescues-defective-mitochondrial-respiration-in-duchenne-muscular-dystrophy
#5
Marco Schiavone, Alessandra Zulian, Sara Menazza, Valeria Petronilli, Francesco Argenton, Luciano Merlini, Patrizia Sabatelli, Paolo Bernardi
Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP). Treatment with the cyclophilin inhibitor alisporivir - a cyclosporin A derivative that desensitizes the PTP but does not inhibit calcineurin - largely restored the maximal respiratory capacity without affecting basal oxygen consumption in cells from patients, thus reinstating a normal respiratory reserve...
September 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#6
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28871039/human-torsina-can-function-in-the-yeast-cytosol-as-a-molecular-chaperone
#7
Ilectra Adam, Lyne Jossé, Mick F Tuite
TorsinA (TorA) is an AAA+ ATPAse linked to dystonia type 1 (DYT1), a neurological disorder that leads to uncontrollable muscular movements. Although DYT1 is linked to a 3bp deletion in the C terminus of TorA, the biological function of TorA remains to be established. Here we use the yeast Saccharomyces cerevisiae as a tractable in vivo model to explore TorA function. We demonstrate that TorA can protect yeast cells against different forms of environmental stress and show that in the absence of the molecular disaggregase Hsp104, TorA can refold heat-denatured luciferase in vivo in an ATP-dependent manner...
September 4, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28851655/dp71-is-regulated-by-phosphorylation-and-ubiquitin-proteasome-system-in-neuronal-cells
#8
Takahiro Fujimoto, Takeshi Yaoi, Shinji Fushiki, Kyoko Itoh
The Dystrophin (Dp) gene is responsible for Duchenne muscular dystrophy (DMD), which is characterized by progressive muscular degeneration and variable degrees of cognitive impairment. Although Dp71 is the most abundant among the Dp isoforms in the brain, the regulatory mechanisms of the related expression levels have not been elucidated. In this study, we found that the constitutive expression levels of Dp71 in PC12 cells were sensitive to proteasomal inhibition. The ectopic expression of FLAG-tagged ubiquitin revealed that Dp71 was ubiquitinated intracellularly...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28842599/overexpression-of-mir-210-and-its-significance-in-ischemic-tissue-damage
#9
G Zaccagnini, B Maimone, P Fuschi, D Maselli, G Spinetti, C Gaetano, F Martelli
Hypoxia-induced miR-210 displays a pro-survival, cytoprotective and pro-angiogenic role in several in vitro systems. In vivo, we previously found that miR-210 inhibition increases ischemic damage. Here we describe the generation of a versatile transgenic mouse model allowing the evaluation of miR-210 therapeutic potential in ischemic cardiovascular diseases. We generated a Tet-On miR-210 transgenic mouse strain (TG-210) by targeted transgenesis in the ROSA26 locus. To functionally validate miR-210 transgenic mice, hindlimb ischemia was induced by femoral artery dissection...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836095/selenoprotein-n-was-required-for-the-regulation-of-selenium-on-the-uterine-smooth-muscle-contraction-in-mice
#10
Jingxuan Zhou, Chengye Li, Gaoqin Gu, Qi Wang, Mengyao Guo
Selenium (Se) is an essential micronutrient affecting various aspects of health. The balance of the Se concentration has an important protective and promoter effect on physiological function in inducing muscular disorders in smooth muscle. Selenoprotein N (SelN) is closely related to Ca(2+) release. The present study aimed to determine the effects and mechanism of action of dietary Se on uterine smooth muscle contraction via SelN using a mouse model. Quantitative polymerase chain reaction (qPCR) analysis was performed to detect mRNA levels...
August 23, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28829918/ipsilateral-corticomotor-responses-are-confined-to-the-homologous-muscle-following-cross-education-of-muscular-strength
#11
Joel Mason, Ashlyn K Frazer, Deanna M Horvath, Alan J Pearce, Janne Avela, Glyn Howatson, Dawson J Kidgell
Cross-education of strength occurs when strength-training one limb increases the strength of the untrained limb and is restricted to the untrained homologous muscle. Cortical circuits located ipsilateral to the trained limb might be involved. We used transcranial magnetic stimulation (TMS) to determine the corticomotor responses from the untrained homologous (biceps brachii) and non-homologous (flexor carpi radialis) muscle following strength-training of the right elbow flexors. Motor evoked potentials were recorded from the untrained left biceps brachii and flexor carpi radialis during a submaximal contraction from 20 individuals (10 women, 10 men, aged 18-35 years; training group; n = 10 and control group; n = 10) before and after 3-weeks of strength-training the right biceps brachii at 80% of 1-repetition maximum (1-RM)...
August 22, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28826912/edaravone-is-a-candidate-agent-for-spinal-muscular-atrophy-in-vitro-analysis-using-a-human-induced-pluripotent-stem-cells-derived-disease-model
#12
Shiori Ando, Michinori Funato, Kazuki Ohuchi, Tsubasa Kameyama, Satoshi Inagaki, Junko Seki, Chizuru Kawase, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideo Kaneko, Hideaki Hara
Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons...
August 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28817625/disentangling-the-relationship-between-children-s-motor-ability-executive-function-and-academic-achievement
#13
Mirko Schmidt, Fabienne Egger, Valentin Benzing, Katja Jäger, Achim Conzelmann, Claudia M Roebers, Caterina Pesce
Even though positive relations between children's motor ability and their academic achievement are frequently reported, the underlying mechanisms are still unclear. Executive function has indeed been proposed, but hardly tested as a potential mediator. The aim of the present study was therefore to examine the mediating role of executive function in the relationship between motor ability and academic achievement, also investigating the individual contribution of specific motor abilities to the hypothesized mediated linkage to academic achievement...
2017: PloS One
https://www.readbyqxmd.com/read/28810660/recent-advancements-in-understanding-mammalian-o-mannosylation
#14
M Osman Sheikh, Stephanie M Halmo, Lance Wells
The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hypoglycosylation of α-DG results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-DG, primarily glycosyltransferases, are the basis for these diseases...
September 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28808928/regulation-of-survival-motor-neuron-protein-by-the-nuclear-factor-kappa-b-pathway-in-mouse-spinal-cord-motoneurons
#15
Saravanan Arumugam, Stefka Mincheva-Tasheva, Ambika Periyakaruppiah, Sandra de la Fuente, Rosa M Soler, Ana Garcera
Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease...
August 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28808653/acyl-coa-synthetase-5-promotes-the-growth-and-invasion-of-colorectal-cancer-cells
#16
Shihua Ding, Shaohui Tang, Min Wang, Donghai Wu, Haijian Guo
BACKGROUND AND AIMS: Acyl-CoA synthetase 5 (ACS5) has been reported to be associated with the development of various cancers, but the role of it in colorectal cancer (CRC) is not well understood. The present study aimed to explore the potential role of ACS5 in the development and progression of CRC. METHODS: ACS5 expression in CRC tissues and CRC cell lines was examined, and its clinical significance was analyzed. The role of ACS5 in cell proliferation, apoptosis, and invasion was examined in vitro...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28796387/ulinastatin-inhibited-sepsis-induced-spinal-inflammation-to-alleviate-peripheral-neuromuscular-dysfunction-in-an-experimental-rat-model-of-neuromyopathy
#17
Fei Xie, Su Min, Jingyuan Chen, Jun Yang, Xin Wang
Sepsis initiates a neuroinflammatory cascade that contributes to spinal cord inflammation and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In this study, we tested the hypothesis that ulinastatin (ULI) inhibits sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction through the TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB signaling pathway. Muscular function, spinal cord water content, and cytokine levels of spinal cord were tested in TLR4-inhibited rats subjected to cecal ligation and puncture (CLP)...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28790171/the-ror1-receptor-tyrosine-kinase-plays-a-critical-role-in-regulating-satellite-cell-proliferation-during-regeneration-of-injured-muscle
#18
Koki Kamizaki, Ryosuke Doi, Makoto Hayashi, Takeshi Saji, Motoi Kanagawa, Tatsushi Toda, So-Ichiro Fukada, Hsin-Yi Henry Ho, Michael Eldon Greenberg, Mitsuharu Endo, Yasuhiro Minami
The Ror family receptor tyrosine kinases, Ror1 and Ror2 play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remains largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury, and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles...
August 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28780350/effect-of-elovl3-expression-on-bovine-skeletal-muscle-derived-satellite-cell-differentiation
#19
Dan Liu, Jia-Hui Xu, Hui-Li Tong, Shu-Feng Li, Yun-Qin Yan
ELOVL3 is involved in elongating saturated and monounsaturated fatty acids, and is a critical enzyme for lipid accumulation in brown adipocytes during the early phase of tissue recruitment. In addition, ELOVL3 is related to increased fatty acid oxidation in brown adipocytes. However, the potential functions of ELOVL3 in bovine cells remain unclear. Herein, we aimed to elucidate the effect of the ELOVL3 on the differentiation of bovine skeletal muscle-derived satellite cells (MDSCs). Western blot and immunofluorescence analyses were used for elucidating ELOVL3 expression pattern in bovine MDSCs during differentiation in vitro...
August 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28763302/intramuscularly-injected-neurotropin-reduced-muscular-mechanical-hyperalgesia-induced-by-repeated-cold-stress-in-rats
#20
Teruaki Nasu, Shiori Murase, Yoshiko Takeda-Uchimura, Kazue Mizumura
An extract of rabbit skin inflamed by inoculation with the vaccinia virus, neurotropin [by intravenous, oral, and intramuscular (i.m.) administration], has been used in China and Japan for the treatment of chronic pain. In this study, we investigated the analgesic mechanism of i.m. neurotropin. Rats were exposed to repeated cold stress, and muscular mechanical hyperalgesia was evaluated by measuring the withdrawal threshold of the gastrocnemius muscle using Randall-Selitto apparatus. I.m. but not subcutaneous, neurotropin dose dependently reduced the repeated cold stress-induced muscular mechanical hyperalgesia for 3 h, but it had no effect in normal rats...
July 31, 2017: Behavioural Pharmacology
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