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JOURNAL ARTICLE
Sandra Donkervoort, Martijn van de Locht, Dario Ronchi, Janine Reunert, Catriona A McLean, Maha Zaki, Rotem Orbach, Josine M de Winter, Stefan Conijn, Daan Hoomoedt, Osorio Lopes Abath Neto, Francesca Magri, Angela N Viaene, A Reghan Foley, Svetlana Gorokhova, Véronique Bolduc, Ying Hu, Nicole Acquaye, Laura Napoli, Julien H Park, Kalyan Immadisetty, Lee B Miles, Mona Essawi, Salar McModie, Leonardo F Ferreira, Simona Zanotti, Sarah B Neuhaus, Livija Medne, Nagham ElBagoury, Kory R Johnson, Yong Zhang, Nigel G Laing, Mark R Davis, Robert J Bryson-Richardson, Darren T Hwee, James J Hartman, Fady I Malik, Peter M Kekenes-Huskey, Giacomo Pietro Comi, Wessam Sharaf-Eldin, Thorsten Marquardt, Gianina Ravenscroft, Carsten G Bönnemann, Coen A C Ottenheijm
Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast ( TNNI2 ) and TnI-slow ( TNNI1 ), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare cause of arthrogryposis, whereas TNNI1 variants have not been conclusively established to cause skeletal myopathy. We identified recessive loss-of-function TNNI1 variants as well as dominant gain-of-function TNNI1 variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms...
April 3, 2024: Science Translational Medicine
#2
JOURNAL ARTICLE
Li Chen, Yan Chen, Mengxia Wang, Linglin Lai, Linbo Zheng, Huiqin Lu
Cancer cachexia, a multi-organ disorder resulting from tumor and immune system interactions, prominently features muscle wasting and affects the survival of patients with cancer. Ursolic acid (UA) is known for its antioxidant, anti-inflammatory, and anticancer properties. However, its impact on cancer cachexia remains unexplored. This study aimed to assess the efficacy of UA in addressing muscle atrophy and organ dysfunction in cancer cachexia and reveal the mechanisms involved. UA dose-dependently ameliorated C2C12 myotube atrophy...
February 27, 2024: European Journal of Pharmacology
#3
JOURNAL ARTICLE
Ricardo A Galli, Tamara C Borsboom, Charlotte Gineste, Lorenza Brocca, Maira Rossi, Darren T Hwee, Fady I Malik, Roberto Bottinelli, Julien Gondin, Maria-Antonietta Pellegrino, Josine M de Winter, Coen A C Ottenheijm
Nemaline myopathies are the most common form of congenital myopathies. Variants in ACTA1 (NEM3) comprise 15-25% of all nemaline myopathy cases. Patients harboring variants in ACTA1 present with a heterogeneous disease course characterized by stable or progressive muscle weakness and, in severe cases, respiratory failure and death. To date, no specific treatments are available. Since NEM3 is an actin-based thin filament disease, we tested the ability of tirasemtiv, a fast skeletal muscle troponin activator, to improve skeletal muscle function in a mouse model of NEM3, harboring the patient-based p...
April 1, 2024: Journal of General Physiology
#4
JOURNAL ARTICLE
Katarzyna Robaszkiewicz, Małgorzata Siatkowska, Renske I Wadman, Erik-Jan Kamsteeg, Zhiyong Chen, Ashirwad Merve, Matthew Parton, Enrico Bugiardini, Charlotte de Bie, Joanna Moraczewska
A novel variant of unknown significance c.8A > G (p.Glu3Gly) in TPM3 was detected in two unrelated families. TPM3 encodes the transcript variant Tpm3.12 (NM_152263.4), the tropomyosin isoform specifically expressed in slow skeletal muscle fibers. The patients presented with slowly progressive muscle weakness associated with Achilles tendon contractures of early childhood onset. Histopathology revealed features consistent with a nemaline rod myopathy. Biochemical in vitro assays performed with reconstituted thin filaments revealed defects in the assembly of the thin filament and regulation of actin-myosin interactions...
November 9, 2023: International Journal of Molecular Sciences
#5
JOURNAL ARTICLE
Johanna Giers, Alexander Bartel, Katharina Kirsch, Simon Franz Müller, Stephanie Horstmann, Heidrun Gehlen
Horses competing in cross-country tests are subjected to high physical demands. Within the scope of this prospective longitudinal study, blood values of 20 elite eventing horses were examined before and after two- to four-star cross-country rides. The aim was to find out whether blood-based markers for skeletal muscle and cardiac muscle function change after cross-country exercise. Parameters that provide information about fluid balance, muscle enzymes, metabolites and cardiac muscle-specific markers were investigated...
October 5, 2023: Animals: An Open Access Journal From MDPI
#6
JOURNAL ARTICLE
Song Gao, Shuai Zhuang, Longteng Zhang, René Lametsch, Yuqing Tan, Bo Li, Hui Hong, Yongkang Luo
Protein degradation and oxidation are two major alterations during the storage of processed bighead carp fillets. This study conducted a comparative analysis of degraded and oxidized products as well as oxidation sites in fresh, frozen and brined frozen bighead carp fillets. Frozen storage played a dominant role in protein degradation and oxidation, and brining promoted these changes. In brined frozen samples, the decreased SDS-PAGE band intensities for tropomyosin, troponin, and myosin light chain were mainly due to their degradation...
September 1, 2023: Food Chemistry
#7
REVIEW
Oksana P Gerzen, Veronika O Votinova, Iulia K Potoskueva, Alyona E Tzybina, Larisa V Nikitina
The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg2+ and Ca2+ . In skeletal Troponin C, Cd2+ , Sr2+ , Pb2+ , Mn2+ , Co2+ , Ni2+ , Ba2+ , Mg2+ , Zn2+ , and trivalent lanthanides can substitute for Ca2+ ...
June 24, 2023: International Journal of Molecular Sciences
#8
JOURNAL ARTICLE
Josué Orozco-Aguilar, Franco Tacchi, Francisco Aguirre, Mayalen Valero-Breton, Mauricio Castro-Sepulveda, Felipe Simon, Claudio Cabello-Verrugio
BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations...
May 27, 2023: Biological Research
#9
JOURNAL ARTICLE
Eric R Hantz, Svetlana B Tikunova, Natalya Belevych, Jonathan P Davis, Peter J Reiser, Steffen Lindert
Despite large investments from academia and industry, heart failure, which results from a disruption of the contractile apparatus, remains a leading cause of death. Cardiac muscle contraction is a calcium-dependent mechanism, which is regulated by the troponin protein complex (cTn) and specifically by the N-terminal domain of its calcium-binding subunit (cNTnC). There is an increasing need for the development of small molecules that increase calcium sensitivity without altering the systolic calcium concentration, thereby strengthening the cardiac function...
May 19, 2023: Journal of Chemical Information and Modeling
#10
JOURNAL ARTICLE
Arnold Tan, Awais Z Younis, Alexander Evans, Jade V Creighton, Clare Coveny, David J Boocock, Craig Sale, Gareth G Lavery, Amanda S Coutts, Craig L Doig
The ADP-ribosyltransferase, PARP1 enzymatically generates and applies the post-translational modification, ADP-Ribose (ADPR). PARP1 roles in genome maintenance are well described, but recent work highlights roles in many fundamental processes including cellular identity and energy homeostasis. Herein, we show in both mouse and human skeletal muscle cells that PARP1-mediated PARylation is a regulator of the myogenic program and the muscle transcriptional response to steroid hormones. Chemical PARP1 modulation impacts the expression of major myocellular proteins, including troponins, key in dictating muscle contractile force...
April 22, 2023: Cell Death Discovery
#11
JOURNAL ARTICLE
Laurin M Hanft, Joel C Robinett, Theodore J Kalogeris, Kenneth S Campbell, Brandon J Biesiadecki, Kerry S McDonald
The heart's pumping capacity is determined by myofilament power generation. Power is work done per unit time and measured as the product of force and velocity. At a sarcomere level, these contractile properties are linked to the number of attached cross-bridges and their cycling rate, and many signaling pathways modulate one or both factors. We previously showed that power is increased in rodent permeabilized cardiac myocytes following PKA-mediated phosphorylation of myofibrillar proteins. The current study found that that PKA increased power by ∼30% in permeabilized cardiac myocyte preparations (n = 8) from human failing hearts...
May 1, 2023: Journal of General Physiology
#12
JOURNAL ARTICLE
Abdul Rashid Issahaku, Mahmoud A A Ibrahim, Namutula Mukelabai, Mahmoud E S Soliman
Muscle weakness as a secondary feature of attenuated neuronal input often leads to disability and sometimes death in patients with neurogenic neuromuscular diseases. These impaired muscle function has been observed in several diseases including amyotrophic lateral sclerosis, Charcot-Marie-Tooth, spinal muscular atrophy and Myasthenia gravis. This has spurred the search for small molecules which could activate fast skeletal muscle troponin complex as a means to increase muscle strength. Discovered small molecules have however been punctuated by off-target and side effects leading to the development of the second-generation small molecule, Reldesemtiv...
March 23, 2023: Protein Journal
#13
JOURNAL ARTICLE
Mengyang Liu, Ying Lin, Lingya Qiao, Juan Chen, Qiang Shi
OBJECTIVE: To investigate the characteristics of cardiac involvement due to Immune-mediated Necrotizing Myopathy (IMNM). METHODS: Patients diagnosed with Immune-mediated Necrotizing Myopathy (IMNM) who attended the Department of Neurology and the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital between February 2011 and June 2022 were collected. Clinicopathological diagnosis of IMNM was performed according to the criteria established by the European Neuromuscular Center (ENMC)...
2023: Frontiers in Immunology
#14
JOURNAL ARTICLE
Jianhong Sun, Sheng Ye, Geng Yin, Qibing Xie
OBJECTIVES: N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles, however, its value in patients with IIM is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. METHODS: Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage...
March 15, 2023: Rheumatology
#15
JOURNAL ARTICLE
Muneeb Iqbal, Edward Bliss, Eliza Whiteside, Ben Hoffman, Dean E Mills
Elevated respiratory muscle work is encountered during strenuous exercise, acute and chronic respiratory disorders and during inspiratory pressure-threshold loading (ITL). ITL can induce respiratory muscle damage, evidenced by increases in fast and slow skeletal troponin-I (sTnI). However, other blood markers of muscle damage have not been measured. We investigated respiratory muscle damage following ITL using a skeletal muscle damage biomarkers panel. Seven healthy men (33±2 years) undertook 60 min of ITL at a resistance equivalent to ~0% (Sham ITL) and 70% of their maximal inspiratory pressure two weeks apart...
March 2, 2023: Journal of Applied Physiology
#16
REVIEW
Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs.
Taejeong Song, Maicon Landim-Vieira, Mustafa Ozdemir, Caroline Gott, Onur Kanisicak, Jose Renato Pinto, Sakthivel Sadayappan
Skeletal muscle, a highly complex muscle type in the eukaryotic system, is characterized by different muscle subtypes and functions associated with specific myosin isoforms. As a result, skeletal muscle is the target of numerous diseases, including distal arthrogryposes (DAs). Clinically, DAs are a distinct disorder characterized by variation in the presence of contractures in two or more distal limb joints without neurological issues. DAs are inherited, and up to 40% of patients with this condition have mutations in genes that encode sarcomeric protein, including myosin heavy chains, troponins, and tropomyosin, as well as myosin binding protein-C (MYBPC)...
March 2023: Experimental & Molecular Medicine
#17
Eric R Hantz, Svetlana B Tikunova, Natalya Belevych, Jonathan P Davis, Peter J Reiser, Steffen Lindert
Despite large investments from academia and industry, heart failure, which results from a disruption of the contractile apparatus, remains a leading cause of death. Cardiac muscle contraction is a calcium-dependent mechanism, which is regulated by the troponin protein complex (cTn) and specifically by the N-terminal domain of its calcium binding subunit (cNTnC). There is an increasing need for the development of small molecules that increase calcium sensitivity without altering systolic calcium concentration, thereby strengthening cardiac function...
February 6, 2023: bioRxiv
#18
JOURNAL ARTICLE
Elena A Zvereva, Olga D Hendrickson, Boris B Dzantiev, Anatoly V Zherdev
Assessment of the composition of meat-containing products is the task in demand due to their frequent deviations from declared recipes. The paper presents the developed test system for immunochromatographic determination of total meat content. The assay is based on the simultaneous use of monoclonal antibodies, which specifically interacts with mammalian skeletal troponin I, and polyclonal antibodies, which specifically detect bird immunoglobulin Y. To integrate the detection of both types of meat by the same test strip, the antibodies are mixed in the analytical zone of the test strip and in complex with a gold nanoparticle label...
December 12, 2022: Sensors
#19
JOURNAL ARTICLE
Yunpeng Li, Tong Zhou, Junyi Zhuang, Yingying Dai, Xiyu Zhang, Shaocheng Bai, Bohao Zhao, Xianwei Tang, Xinsheng Wu, Yang Chen
While restricting nutrition can improve diseases related to the digestive tract, excessive restriction of food intake can also lead to malnutrition and delayed physical growth. Therefore, this brings the demand to study the effect and potential mechanism of restricted feeding on skeletal muscle development in rabbits. This study utilized hematoxylin-eosin (HE) staining to detect muscle fiber area which depicted significant reduction in skeletal muscle fiber upon 30% feed restriction ( p < 0...
December 15, 2022: Animal Biotechnology
#20
Beibei Yin, Junjuan Xiao, Xuan Wang, Xingyu Li, Yaping Guan, Jinghua Chen, Pengxi Han, Kun Li, Jun Wang
Immunotherapy with programmed death 1 (PD-1) inhibitor has shown activity as first- or second-line treatment for various metastatic human malignancies. Immune-related adverse events (irAEs) are now well-described, and most organ sites are potentially influenced, but the prevalence of myocarditis and myositis/myasthenia gravis (MG) overlap syndrome following esophageal hiatal hernia induced by immunotherapy is rarely reported. Here, we describe a 71-year-old woman with a progressed unresectable extrahepatic cholangiocarcinoma and biliary obstruction...
2022: Frontiers in Medicine
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