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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
Frederico Gerlinger-Romero, Caio Yogi Yonamine, Danilo Correa Pinto Junior, João Victor DelConti Esteves, Ubiratan Fabres Machado
Diabetes mellitus (DM) induces a variable degree of muscle sarcopenia, which may be related to protein degradation and to the expression of both E3 ubiquitin ligases and some specific microRNAs (miRNAs). The present study investigated the effect of diabetes and acute muscle contraction upon the TRIM63 and FBXO32 expression as well as the potential involvement of some miRNAs. Diabetes was induced by streptozotocin and studied after 30 days. Soleus muscles were harvested, stimulated to contract in vitro for twitch tension analysis (0...
March 2017: Molecular and Cellular Biochemistry
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
Qiaoli Li, Annerose Berndt, Beth A Sundberg, Kathleen A Silva, Victoria E Kennedy, Clinton L Cario, Matthew A Richardson, Thomas H Chase, Paul N Schofield, Jouni Uitto, John P Sundberg
Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains...
June 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Yannick von Grabowiecki, Paula Abreu, Orphee Blanchard, Lavinia Palamiuc, Samir Benosman, Sophie Mériaux, Véronique Devignot, Isabelle Gross, Georg Mellitzer, José L Gonzalez de Aguilar, Christian Gaiddon
Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice...
February 26, 2016: ELife
Robert M Akscyn, John L Franklin, Tatyana A Gavrikova, Joseph L Messina
Polytrauma is a combination of injuries to more than one body part or organ system. Polytrauma is common in warfare, and in automobile and industrial accidents. The combination of injuries can include burn, fracture, hemorrhage, and trauma to the extremities or specific organ systems. Resistance to anabolic hormones, loss of muscle mass, and metabolic dysfunction can occur following injury. To investigate the effects of combined injuries, we have developed a highly reproducible rodent model of polytrauma. This model combines burn injury, soft tissue trauma, and penetrating injury to the gastrointestinal (GI) tract...
February 2016: Physiological Reports
Florian Rambow, Bastien Job, Valérie Petit, Franck Gesbert, Véronique Delmas, Hannah Seberg, Guillaume Meurice, Eric Van Otterloo, Philippe Dessen, Caroline Robert, Daniel Gautheret, Robert A Cornell, Alain Sarasin, Lionel Larue
Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA), a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases...
October 27, 2015: Cell Reports
Yanqing Liu, Yueqiu Wang, Nailong Yang, Suning Wu, Yanhua Lv, Lili Xu
Postmenopausal osteoporosis (PO) is a common disease in females >50 years of age worldwide and is becoming an increasing burden to society. The present study aimed to assess the molecular mechanism of PO using bioinformatic methods. The gene expression data from patients with PO and normal controls were downloaded from the ArrayExpress database provided by European Bioinformatics Institute. Following the screening of the differentially expressed genes (DEGs) using the Limma package in R language, Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tools...
November 2015: Molecular Medicine Reports
Julius Bogomolovas, Kathrin Brohm, Jelena Čelutkienė, Giedrė Balčiūnaitė, Daiva Bironaitė, Virginija Bukelskienė, Dainius Daunoravičus, Christian C Witt, Jens Fielitz, Virginija Grabauskienė, Siegfried Labeit
Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive left ventricular remodeling whose clinical manifestations and molecular basis are poorly understood. We aimed to evaluate the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage IDCM. Expression patterns of 8 mechanoptotic machinery-associated titin ligands (ANKRD1, ANKRD2, TRIM63, TRIM55, NBR1, MLP, FHL2, and TCAP) were quantitated in endomyocardial biopsies from 25 patients with advanced IDCM...
2015: BioMed Research International
Lanlan Yin, Sergio G Coelho, Julio C Valencia, Dominik Ebsen, Andre Mahns, Christoph Smuda, Sharon A Miller, Janusz Z Beer, Ludger Kolbe, Vincent J Hearing
More than 375 genes have been identified that are involved in regulating skin pigmentation and these act during development, survival, differentiation, and/or responses of melanocytes to the environment. Many of these genes have been cloned, and disruptions of their functions are associated with various pigmentary diseases; however, many remain to be identified. We have performed a series of microarray analyses of hyperpigmented compared with less pigmented skin to identify genes responsible for these differences...
October 2015: Journal of Investigative Dermatology
Montse Olivé, Saba Abdul-Hussein, Anders Oldfors, José González-Costello, Peter F M van der Ven, Dieter O Fürst, Laura González, Dolores Moreno, Benjamín Torrejón-Escribano, Josefina Alió, Adolf Pou, Isidro Ferrer, Homa Tajsharghi
Protein aggregate myopathies (PAMs) define muscle disorders characterized by protein accumulation in muscle fibres. We describe a new PAM in a patient with proximal muscle weakness and hypertrophic cardiomyopathy, whose muscle fibres contained inclusions containing myosin and myosin-associated proteins, and aberrant distribution of microtubules. These lesions appear as intact A- and M-bands lacking thin filaments and Z-discs. These features differ from inclusions in myosin storage myopathy (MSM), but are highly similar to those in mice deficient for the muscle-specific RING finger proteins MuRF1 and MuRF3...
July 1, 2015: Human Molecular Genetics
Peter Tontonoz, Omar Cortez-Toledo, Kevin Wroblewski, Cynthia Hong, Laura Lim, Rogelio Carranza, Orla Conneely, Daniel Metzger, Lily C Chao
We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely, mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and myofiber size...
April 2015: Molecular and Cellular Biology
Qiu-Yue Han, Hong-Xia Wang, Xiao-Hong Liu, Cai-Xia Guo, Qi Hua, Xiao-Hong Yu, Nan Li, Yan-Zong Yang, Jie Du, Yun-Long Xia, Hui-Hua Li
Ubiquitin ligase (E3) is a decisive element of the ubiquitin-proteasome system (UPS), which is the main pathway for intracellular protein turnover. Recently, circulating E3 ligases have been increasingly considered as cancer biomarkers. In the present study, we aimed to determine if cardiac-specific E3 ligases in circulation can serve as novel predictors for early diagnosis of acute myocardial infarction (AMI). By screening and verifying their tissue expression patterns with microarray and real-time PCR analysis, six of 261 E3 ligases, including cardiac-specific Rnf207 and cardiac- and muscle-enriched Fbxo32/atrogin-1, Trim54/MuRF3, Trim63/MuRF1, Kbtbd10/KLHL41, Asb11 and Asb2 in mouse heart, were selected for the present study...
June 2015: Clinical Science (1979-)
Marie-Claude Perry, Catherine R Dufour, Ingrid S Tam, Wafa B'chir, Vincent Giguère
Muscle fitness is an important determinant of health and disease. However, the molecular mechanisms involved in the coordinate regulation of the metabolic and structural determinants of muscle endurance are still poorly characterized. Herein, we demonstrate that estrogen-related receptor α (ERRα, NR3B1) is essential for skeletal muscle fitness. Notably, we show that ERRα-null animals are hypoactive and that genetic or therapeutic disruption of ERRα in mice results in reduced exercise tolerance. Mice lacking ERRα also exhibited lactatemia at exhaustion...
December 2014: Molecular Endocrinology
Wei Li, Mark D Claypool, Annabelle M Friera, John McLaughlin, Kristen A Baltgalvis, Ira J Smith, Taisei Kinoshita, Kathy White, Wayne Lang, Guillermo Godinez, Donald G Payan, Todd M Kinsella
Numerous human diseases can lead to atrophy of skeletal muscle, and loss of this tissue has been correlated with increased mortality and morbidity rates. Clinically addressing muscle atrophy remains an unmet medical need, and the development of preclinical tools to assist drug discovery and basic research in this effort is important for advancing this goal. In this report, we describe the development of a bioluminescent gene reporter rat, based on the zinc finger nuclease-targeted insertion of a bicistronic luciferase reporter into the 3' untranslated region of a muscle specific E3 ubiquitin ligase gene, MuRF1 (Trim63)...
2014: PloS One
Benjamin C Yaden, Yan X Wang, Jonathan M Wilson, Alexander E Culver, Andrea Milner, Amita Datta-Mannan, Pamela Shetler, Johnny E Croy, Guoli Dai, Venkatesh Krishnan
Activin A, a member of the transforming growth factor-β superfamily, provides pleiotropic regulation of fibrosis and inflammation. We aimed at determining whether selective inhibition of activin A would provide a regenerative benefit. The introduction of activin A into normal muscle increased the expression of inflammatory and muscle atrophy genes Tnf, Tnfrsf12a, Trim63, and Fbxo32 by 3.5-, 10-, 2-, and 4-fold, respectively. The data indicate a sensitive response of muscle to activin A. Two hours after cardiotoxin-induced muscle damage, local activin A protein expression increased by threefold to ninefold...
April 2014: American Journal of Pathology
Rafal Ploski, Agnieszka Pollak, Sonja Müller, Maria Franaszczyk, Ewa Michalak, Joanna Kosinska, Piotr Stawinski, Mateusz Spiewak, Hubert Seggewiss, Zofia T Bilinska
RATIONALE: Variants in TRIM63, including a nonsense mutation (p.Q247X), have been suggested recently to cause hypertrophic cardiomyopathy. OBJECTIVE: To verify pathogenicity of TRIM63 p.Q247X detected by whole-exome sequencing in a symptomless professional sports player seeking medical advice because of a prolonged QT interval found during a routine check-up. METHODS AND RESULTS: Clinical studies were performed in the proband and his mother, who also carried TRIM63 p...
January 17, 2014: Circulation Research
Reiko Nakao, Saori Yamamoto, Yuki Yasumoto, Katsutaka Oishi
Many inflammatory and autoimmune diseases are treated using synthetic glucocorticoids. However, excessive glucocorticoid can often cause unpredictable effects including muscle atrophy. Endogenous glucocorticoid levels robustly fluctuate in a circadian manner and peak just before the onset of the active phase in both humans and nocturnal rodents. The present study determines whether muscle atrophy induced by exogenous glucocorticoid can be avoided by optimizing dosing times. We administered single daily doses of the glucocorticoid analog dexamethasone (Dex) to mice for 10 days at the times of day corresponding to peak (early night) or trough (early morning) endogenous glucocorticoid levels...
May 2014: Chronobiology International
Muzamil Majid Khan, Siegfried Strack, Franziska Wild, Akira Hanashima, Alexander Gasch, Kathrin Brohm, Markus Reischl, Silvia Carnio, Dittmar Labeit, Marco Sandri, Siegfried Labeit, Rüdiger Rudolf
Removal of ubiquitinated targets by autophagosomes can be mediated by receptor molecules, like SQSTM1, in a mechanism referred to as selective autophagy. While cytoplasmic protein aggregates, mitochondria, and bacteria are the best-known targets of selective autophagy, their role in the turnover of membrane receptors is scarce. We here showed that fasting-induced wasting of skeletal muscle involves remodeling of the neuromuscular junction (NMJ) by increasing the turnover of muscle-type CHRN (cholinergic receptor, nicotinic/nicotinic acetylcholine receptor) in a TRIM63-dependent manner...
January 2014: Autophagy
Xiaochu Zhang, Amy M Sharma, Jack Uetrecht
Nevirapine (NVP) can cause serious skin rashes and hepatotoxicity. It also causes an immune-mediated skin rash in rats but not hepatotoxicity. This rash is caused by a metabolite of NVP; specifically, NVP is oxidized in the liver to a benzylic alcohol (12-OH-NVP), which travels to the skin where it forms a reactive benzylic sulfate. This could both act as a hapten and induce a danger signal. In contrast, most of the covalent binding in the liver involves oxidation of the methyl group leading to a reactive quinone methide...
September 16, 2013: Chemical Research in Toxicology
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