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Skeletal muscle-specific troponin

Ajay D Verma, Veena K Parnaik
Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans...
July 2017: Cell Biology International
Lorenza Brocca, Jamie S McPhee, Emanuela Longa, Monica Canepari, Olivier Seynnes, Giuseppe De Vito, Maria Antonietta Pellegrino, Marco Narici, Roberto Bottinelli
KEY POINTS: Loss of muscle mass and strength in the growing population of elderly people is a major health concern for modern societies. This condition, termed sarcopenia, is a major cause of falls and of the subsequent increase in morbidity and mortality. Despite numerous studies on the impact of ageing on individual muscle fibres, the contribution of single muscle fibre adaptations to ageing-induced atrophy and functional impairment is still unsettled. The level of physical function and disuse is often associated with ageing...
July 15, 2017: Journal of Physiology
Zherong Xu, Xin Feng, Juan Dong, Zhong-Min Wang, Jingyun Lee, Cristina Furdui, Daniel Clark Files, Kristen M Beavers, Stephen Kritchevsky, Carolanne Milligan, Jian-Ping Jin, Osvaldo Delbono, Tan Zhang
BACKGROUND: Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia...
April 16, 2017: Journal of Cachexia, Sarcopenia and Muscle
Sergey Y Bershitsky, Natalia A Koubassova, Michael A Ferenczi, Galina V Kopylova, Theyencheri Narayanan, Andrey K Tsaturyan
Muscle contraction is powered by actin-myosin interaction controlled by Ca(2+) via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin filament. In the absence of Ca(2+), Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in the blocked, or B, state, where Tpm shields actin from the binding of myosin heads. Ca(2+) binding to Tn releases the Tpm from actin so that it moves azimuthally around the filament axis to a closed, or C, state, where actin is partially available for weak binding of myosin heads...
April 11, 2017: Biophysical Journal
Brian Leei Lin, Taejeong Song, Sakthivel Sadayappan
Striated cardiac and skeletal muscles play very different roles in the body, but they are similar at the molecular level. In particular, contraction, regardless of the type of muscle, is a precise and complex process involving the integral protein myofilaments and their associated regulatory components. The smallest functional unit of muscle contraction is the sarcomere. Within the sarcomere can be found a sophisticated ensemble of proteins associated with the thick filaments (myosin, myosin binding protein-C, titin, and obscurin) and thin myofilaments (actin, troponin, tropomyosin, nebulin, and nebulette)...
March 16, 2017: Comprehensive Physiology
Katerina Vlasakova, Pamela Lane, Laura Michna, Nagaraja Muniappa, Frank D Sistare, Warren E Glaab
The skeletal muscle (SKM) injury biomarkers, skeletal troponin I (sTnI), myosin light chain 3 (Myl3), and creatine kinase muscle isoform (Ckm) have been shown recently to be more sensitive and specific for monitoring drug-induced SKM injury than the conventional biomarkers, aspartate transaminase (AST) and creatine kinase (CK) enzymatic assays in rat toxicology studies. To evaluate the utility of these SKM biomarkers across species, they were assessed in 2 dog models: a drug-induced injury study in Beagle dogs and a 160 km endurance exercise run completed by Alaskan sled dogs...
April 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Han-Zhong Feng, J-P Jin
Carbonic anhydrase III (CAIII) is a metabolic enzyme and a regulator for intracellular pH. CAIII has been reported with high level expression in slow twitch skeletal muscles. Here we demonstrate that CAIII is expressed in multiple slow and fast twitch muscles of adult mouse independent of the expression of myosin isoforms. Expressing similar fast type of myofilament proteins, CAIII-positive tibial anterior (TA) muscle exhibits higher tolerance to fatigue than that of CAIII-negative fast twitch extensor digitorum longus (EDL) muscle in in situ contractility studies...
2016: Frontiers in Physiology
Fangze Cai, Monica X Li, Sandra E Pineda-Sanabria, Shorena Gelozia, Steffen Lindert, Frederick West, Brian D Sykes, Peter M Hwang
In cardiac and skeletal muscle, the troponin complex turns muscle contraction on and off in a calcium-dependent manner. Many small molecules are known to bind to the troponin complex to modulate its calcium binding affinity, and this may be useful in a broad range of conditions in which striated muscle function is compromised, such as congestive heart failure. As a tool for developing drugs specific for the cardiac isoform of troponin, we have designed a chimeric construct (cChimera) consisting of the regulatory N-terminal domain of cardiac troponin C (cNTnC) fused to the switch region of cardiac troponin I (cTnI), mimicking the key binding event that turns on muscle contraction...
December 2016: Journal of Molecular and Cellular Cardiology
Jie Liu, Ruiqi Fu, Ranran Liu, Guiping Zhao, Maiqing Zheng, Huanxian Cui, Qinghe Li, Jiao Song, Jie Wang, Jie Wen
Muscle development and growth influences the efficiency of poultry meat production, and is closely related to deposition of intramuscular fat (IMF), which is crucial in meat quality. To clarify the molecular mechanisms underlying muscle development and IMF deposition in chickens, protein expression profiles were examined in the breast muscle of Beijing-You chickens at ages 1, 56, 98 and 140 days, using isobaric tags for relative and absolute quantification (iTRAQ). Two hundred and four of 494 proteins were expressed differentially...
2016: PloS One
Edward P Debold, Robert H Fitts, Christopher W Sundberg, Thomas M Nosek
The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle's molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin's ability to move actin...
November 2016: Medicine and Science in Sports and Exercise
Charles M Stevens, Kaveh Rayani, Christine E Genge, Gurpreet Singh, Bo Liang, Janine M Roller, Cindy Li, Alison Yueh Li, D Peter Tieleman, Filip van Petegem, Glen F Tibbits
Zebrafish, as a model for teleost fish, have two paralogous troponin C (TnC) genes that are expressed in the heart differentially in response to temperature acclimation. Upon Ca(2+) binding, TnC changes conformation and exposes a hydrophobic patch that interacts with troponin I and initiates cardiac muscle contraction. Teleost-specific TnC paralogs have not yet been functionally characterized. In this study we have modeled the structures of the paralogs using molecular dynamics simulations at 18°C and 28°C and calculated the different Ca(2+)-binding properties between the teleost cardiac (cTnC or TnC1a) and slow-skeletal (ssTnC or TnC1b) paralogs through potential-of-mean-force calculations...
July 12, 2016: Biophysical Journal
C R Lamboley, V L Wyckelsma, B D Perry, M J McKenna, G D Lamb
Inactivity negatively impacts on skeletal muscle function mainly through muscle atrophy. However, recent evidence suggests that the quality of individual muscle fibers is also altered. This study examined the effects of 23 days of unilateral lower limb suspension (ULLS) on specific force and sarcoplasmic reticulum (SR) Ca(2+) content in individual skinned muscle fibers. Muscle biopsies of the vastus lateralis were taken from six young healthy adults prior to and following ULLS. After disuse, the endogenous SR Ca(2+) content was ∼8% lower in type I fibers and maximal SR Ca(2+) capacity was lower in both type I and type II fibers (-11 and -5%, respectively)...
August 1, 2016: Journal of Applied Physiology
Takashi Kondo, Daisuke Kobayashi, Maki Mochizuki, Kouichi Asanuma, Satoshi Takahashi
Background Recently developed reagents for the highly sensitive measurement of cardiac troponin I are useful for early diagnosis of acute coronary syndrome. However, differences in measured values between these new reagents and previously used reagents have not been well studied. In this study, we aimed to compare the values between ARCHITECT High-Sensitive Troponin I ST (newly developed reagents), ARCHITECT Troponin I ST and STACIA CLEIA cardiac troponin I (two previously developed reagent kits). Methods Gel filtration high-performance liquid chromatography was used to analyse the causes of differences in measured values...
January 2017: Annals of Clinical Biochemistry
Sarah Morar Schneider, Amanda Erickson Coleman, Lee-Jae Guo, Sandra Tou, Bruce W Keene, Joe N Kornegay
Golden retriever muscular dystrophy (GRMD) is a model for the genetically homologous human disease, Duchenne muscular dystrophy (DMD). Unlike the mildly affected mdx mouse, GRMD recapitulates the severe DMD phenotype. In addition to skeletal muscle involvement, DMD boys develop cardiomyopathy. While the cardiomyopathy of DMD is typically slowly progressive, rare early episodes of acute cardiac decompensation, compatible with myocardial infarction, have been described. We report here a 7-month-old GRMD dog with an apparent analogous episode of myocardial infarction...
June 2016: Neuromuscular Disorders: NMD
Lara Pes, Young Kim, Ching-Hsuan Tung
Cardiomyocytes are the major component of the heart. Their dysfunction or damage could lead to serious cardiovascular diseases, which have claimed numerous lives around the world. A molecule able to recognize cardiomyocytes would have significant value in diagnosis and treatment. Recently a novel peptide termed myocyte targeting peptide (MTP), with three residues of a non-natural amino acid biphenylalanine (Bip), showed good affinity to cardiomyocytes. Its selectivity towards cardiac tissues was concluded to be due to the ability of Bip to bind cardiac troponin I...
April 15, 2016: Bioorganic & Medicinal Chemistry
Gregory W King, Eduardo L Abreu, An-Lin Cheng, Keyna K Chertoff, Leticia Brotto, Patricia J Kelly, Marco Brotto
Falling is a significant health issue among elderly adults. Given the multifactorial nature of falls, effective balance and fall risk assessment must take into account factors from multiple sources. Here we investigate the relationship between fall risk and a diverse set of biochemical and biomechanical variables including: skeletal muscle-specific troponin T (sTnT), maximal strength measures derived from isometric grip and leg extension tasks, and postural sway captured from a force platform during a quiet stance task...
March 22, 2016: Oncotarget
Tan Zhang, Andrea S Pereyra, Zhong-Min Wang, Alexander Birbrair, Julie A Reisz, Daniel Clark Files, Lina Purcell, Xin Feng, Maria L Messi, Hanzhong Feng, Joseph Chalovich, Jian-Ping Jin, Cristina Furdui, Osvaldo Delbono
Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel α1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function...
June 2016: Aging Cell
Peter M Burch, Oksana Pogoryelova, Richard Goldstein, Donald Bennett, Michela Guglieri, Volker Straub, Kate Bushby, Hanns Lochmüller, Carl Morris
BACKGROUND: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. OBJECTIVE: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. METHOD: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls...
September 2, 2015: Journal of Neuromuscular Diseases
Laurin M Hanft, Timothy D Cornell, Colin A McDonald, Michael J Rovetto, Craig A Emter, Kerry S McDonald
Increased cardiac myocyte contractility by the β-adrenergic system is an important mechanism to elevate cardiac output to meet hemodynamic demands and this process is depressed in failing hearts. While increased contractility involves augmented myoplasmic calcium transients, the myofilaments also adapt to boost the transduction of the calcium signal. Accordingly, ventricular contractility was found to be tightly correlated with PKA-mediated phosphorylation of two myofibrillar proteins, cardiac myosin binding protein-C (cMyBP-C) and cardiac troponin I (cTnI), implicating these two proteins as important transducers of hemodynamics to the cardiac sarcomere...
July 1, 2016: Archives of Biochemistry and Biophysics
Jian-Ping Jin
Troponin T (TnT) is the tropomyosin-binding and thin filament-anchoring subunit of the troponin complex in skeletal and cardiac muscles. At the center of the sarcomeric thin filament regulatory system of striated muscles, TnT plays an essential role in transducing Ca(2+) signals in the regulation of contraction. Having emerged predating the history of vertebrates, TnT has gone through more than 500 million years of evolution that resulted in three muscle-type-specific isoforms and numerous alternative RNA splicing variants...
2016: International Review of Cell and Molecular Biology
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