54 results found
Squire JM, Luther PK, 2019, Mammalian muscle fibers may be simple as well as slow., Journal of General Physiology, Vol: 151, Pages: 1334-1338, ISSN: 0022-1295
Filomena MC, Yamamoto DL, Caremani M, et al., 2019, Myopalladin promotes muscle growth through modulation of the serum response factor pathway, JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, Vol: 11, Pages: 169-194, ISSN: 2190-5991
Burgoyne T, Heumann J, Morris E, et al., 2019, Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle, Proceedings of the National Academy of Sciences, Vol: 116, Pages: 15534-15539, ISSN: 0027-8424
Striated muscle enables movement in all animals by the contraction of myriads of sarcomeres joined end to end by the Z-bands. The contraction is due to tension generated in each sarcomere between overlapping arrays of actin and myosin filaments. At the Z-band, actin filaments from adjoining sarcomeres overlap and are cross-linked in a regular pattern mainly by the protein α-actinin. The Z-band is dynamic, reflected by the 2 regular patterns seen in transverse section electron micrographs; the so-called small-square and basketweave forms. Although these forms are attributed, respectively, to relaxed and actively contracting muscles, the basketweave form occurs in certain relaxed muscles as in the muscle studied here. We used electron tomography and subtomogram averaging to derive the 3D structure of the Z-band in the swimbladder sonic muscle of type I male plainfin midshipman fish (Porichthys notatus), into which we docked the crystallographic structures of actin and α-actinin. The α-actinin links run diagonally between connected pairs of antiparallel actin filaments and are oriented at an angle of about 25° away from the actin filament axes. The slightly curved and flattened structure of the α-actinin rod has a distinct fit into the map. The Z-band model provides a detailed understanding of the role of α-actinin in transmitting tension between actin filaments in adjoining sarcomeres.
Barefield DY, McNamara JW, Lynch TL, et al., 2019, Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 129, Pages: 236-246, ISSN: 0022-2828
Buyandelger B, Mansfield C, Luther P, et al., 2016, ZBTB17 is a novel cardiomyopathy candidate gene and regulates autophagy in the heart, Cardiovascular Research, Vol: 111, Pages: S36-S36, ISSN: 1755-3245
Toepfer CN, Sikkel MB, Caorsi V, et al., 2016, A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation., American Journal of Physiology - Heart and Circulatory Physiology, Vol: 311, Pages: H465-H475, ISSN: 0363-6135
Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic 'compensation' and congestive 'decompensation'. Nothing is known about the ability of un-infarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drive progression of compensation. We hypothesized that enhanced crossbridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared to non-infarcted controls. Isometric force during submaximal activations was raised >2.4-fold, whilst power was 2-fold greater. EM and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein, and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae.
Jacob F, Yonis AY, Cuello F, et al., 2016, Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue, PLOS One, Vol: 11, ISSN: 1932-6203
IntroductionLeft ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism.Methods and ResultsWe studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy).ConclusionThis study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux.
Luther PK, Burgoyne T, Morris E, 2015, Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle, Journal of Molecular Biology, Vol: 427, Pages: 3527-3537, ISSN: 1089-8638
The Z-band in vertebrate striated muscle crosslinks actin filaments of opposite polarity from adjoiningsarcomeres and transmits tension along myofibrils during muscular contraction. It is also the location of anumber of proteins involved in signalling and myofibrillogenesis; mutations in these proteins lead to myopathies.Understanding the high-resolution structure of the Z-band will help us understand its role in muscle contractionand the role of these proteins in the function of muscle. The appearance of the Z-band in transverse-sectionelectron micrographs typically resembles a small-square lattice or a basketweave appearance. In longitudinalsections, the Z-band width varies more with muscle type than species: slow skeletal and cardiac muscles havewider Z-bands than fast skeletal muscles. As the Z-band is periodic, Fourier methods have previously beenused for three-dimensional structural analysis. To cope with variations in the periodic structure of the Z-band, wehave used subtomogram averaging of tomograms of rat cardiac muscle in which subtomograms are extractedand compared and similar ones are averaged. We show that the Z-band comprises four to six layers of links,presumably α-actinin, linking antiparallel overlapping ends of the actin filaments from the adjoining sarcomeres.The reconstruction shows that the terminal 5–7 nm of the actin filaments within the Z-band is devoid of anyα-actinin links and is likely to be the location of capping protein CapZ.
Luther PK, Squire JM, 2014, The intriguing dual lattices of the Myosin filaments in vertebrate striated muscles: evolution and advantage., Biology (Basel), Vol: 3, Pages: 846-865, ISSN: 2079-7737
Myosin filaments in vertebrate striated muscle have a long roughly cylindrical backbone with cross-bridge projections on the surfaces of both halves except for a short central bare zone. In the middle of this central region the filaments are cross-linked by the M-band which holds them in a well-defined hexagonal lattice in the muscle A-band. During muscular contraction the M-band-defined rotation of the myosin filaments around their long axes influences the interactions that the cross-bridges can make with the neighbouring actin filaments. We can visualise this filament rotation by electron microscopy of thin cross-sections in the bare-region immediately adjacent to the M-band where the filament profiles are distinctly triangular. In the muscles of teleost fishes, the thick filament triangular profiles have a single orientation giving what we call the simple lattice. In other vertebrates, for example all the tetrapods, the thick filaments have one of two orientations where the triangles point in opposite directions (they are rotated by 60° or 180°) according to set rules. Such a distribution cannot be developed in an ordered fashion across a large 2D lattice, but there are small domains of superlattice such that the next-nearest neighbouring thick filaments often have the same orientation. We believe that this difference in the lattice forms can lead to different contractile behaviours. Here we provide a historical review, and when appropriate cite recent work related to the emergence of the simple and superlattice forms by examining the muscles of several species ranging back to primitive vertebrates and we discuss the functional differences that the two lattice forms may have.
Hirt MN, Boeddinghaus J, Mitchell A, et al., 2014, Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 74, Pages: 151-161, ISSN: 0022-2828
Smyth E, Solomon A, Vydyanath A, et al., 2014, Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles, Nanotoxicology, Vol: 9, Pages: 356-364, ISSN: 1743-5404
Abstract Nanoparticles (NPs) may come into contact with circulating blood elements including platelets following inhalation and translocation from the airways to the bloodstream or during proposed medical applications. Studies with model polystyrene latex nanoparticles (PLNPs) have shown that NPs are able to induce platelet aggregation in vitro suggesting a poorly defined potential mechanism of increased cardiovascular risk upon NP exposure. We aimed to provide insight into the mechanisms by which NPs may increase cardiovascular risk by determining the impact of a range of concentrations of PLNPs on platelet activation in vitro and in vivo and identifying the signaling events driving NP-induced aggregation. Model PLNPs of varying nano-size (50 and 100 nm) and surface chemistry [unmodified (uPLNP), amine-modified (aPLNP) and carboxyl-modified (cPLNP)] were therefore examined using in vitro platelet aggregometry and an established mouse model of platelet thromboembolism. Most PLNPs tested induced GPIIb/IIIa-mediated platelet aggregation with potencies that varied with both surface chemistry and nano-size. Aggregation was associated with signaling events, such as granule secretion and release of secondary agonists, indicative of conventional agonist-mediated aggregation. Platelet aggregation was associated with the physical interaction of PLNPs with the platelet membrane or internalization. 50 nm aPLNPs acted through a distinct mechanism involving the physical bridging of adjacent non-activated platelets leading to enhanced agonist-induced aggregation in vitro and in vivo. Our study suggests that should they translocate the pulmonary epithelium, or be introduced into the blood, NPs may increase the risk of platelet-driven events by inducing or enhancing platelet aggregation via mechanisms that are determined by their distinct combination of nano-size and surface chemistry.
Torre I, Jeddi M, Amat-Roldan I, et al., 2014, Ultrastructural and electron tomography analyses of cardiac muscle: normal muscle compared to presence and absence of myosin binding protein C-phosphorylation, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
Amat-Roldan I, Torre I, Luther PK, 2014, Molecular model confirms experimental differences on polarization second harmonic signal from cardiac myosin isoforms, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
Burgoyne T, Lewis A, Dewar A, et al., 2014, Characterizing the ultrastructure of primary ciliary dyskinesia transposition defect using electron tomography, CYTOSKELETON, Vol: 71, Pages: 294-301, ISSN: 1949-3584
Craig R, Lee KH, Mun JY, et al., 2014, Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C, PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, Vol: 466, Pages: 425-431, ISSN: 0031-6768
Hirt MN, Boeddinghaus J, Schaaf S, et al., 2014, Maturation of Engineered Heart Tissue (EHT) by Permanent Electrical Stimulation, 80th Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und-Toxikologie-e-V, Publisher: SPRINGER, Pages: S50-S50, ISSN: 0028-1298
Toepfer C, Sikkel M, Caorsi V, et al., 2014, Effects of Chronic Myocardial Infarction on Cardiac Muscle Performance and Structure In-Vivo and In-Vitro, 58th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 343A-344A, ISSN: 0006-3495
Ha K, Buchan JG, Alvarado DM, et al., 2013, MYBPC1 mutations impair skeletal muscle function in zebrafish models of arthrogryposis, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 4967-4977, ISSN: 0964-6906
Squire JM, Guerreiro MJ, Sidebotham RL, et al., 2013, Quantitative MUC5AC and MUC6 mucin estimations in gastric mucus by a least-squares minimization method, ANALYTICAL BIOCHEMISTRY, Vol: 439, Pages: 204-211, ISSN: 0003-2697
Emerson M, Solomon A, Smyth E, et al., 2013, Role of platelets in driving the thrombotic risk and protective processes associated with exposure to diesel exhaust particles, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 643-644, ISSN: 1538-7933
Smyth E, Solomon A, Vydyanath A, et al., 2013, The potencies and mechanisms by which engineered nanoparticles induce platelet aggregation are dependent upon their precise physicochemistry, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 895-896, ISSN: 1538-7933
Solomon A, Smyth E, Mitha N, et al., 2013, Induction of platelet aggregation after a direct physical interaction with diesel exhaust particles, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 325-334, ISSN: 1538-7933
Burgoyne T, Dixon M, Luther P, et al., 2012, Generation of a Three-Dimensional Ultrastructural Model of Human Respiratory Cilia, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 47, Pages: 800-806, ISSN: 1044-1549
Barefield D, Ji X, Zhu G, et al., 2012, Ablation of the Calpain-Targeted Site in Cardiac Myosin Binding Protein-C is Cardioprotective, CIRCULATION, Vol: 126, ISSN: 0009-7322
Sadayappan S, Ji X, Barefield D, et al., 2012, Ablation of Calpain-Targeted Site in Cardiac Myosin Binding Protein C Is Cardioprotective, Basic Cardiovascular Sciences Scientific Session, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7330
Buyandelger B, Luther P, Carrier L, et al., 2012, Pharmacological calcineurin modification improves the phenotype of cardiac myosin binding protein C knockout mice, Conference of the BPS Clinical Pharmacological Section, Publisher: WILEY-BLACKWELL, Pages: 1003-1003, ISSN: 0306-5251
Vydyanath A, Gurnett CA, Marston S, et al., 2012, Axial distribution of myosin binding protein-C is unaffected by mutations in human cardiac and skeletal muscle, Journal of Muscle Research and Cell Motility, Vol: 33, Pages: 61-74, ISSN: 1573-2657
Myosin binding protein-C (MyBP-C), a majorthick filament associated sarcomeric protein, plays animportant functional and structural role in regulating sarcomereassembly and crossbridge formation. Missing oraberrant MyBP-C proteins (both cardiac and skeletal) havebeen shown to cause both cardiac and skeletal myopathies,thereby emphasising its importance for the normal functioningof the sarcomere. Mutations in cardiac MyBP-C area major cause of hypertrophic cardiomyopathy (HCM),while mutations in skeletal MyBP-C have been implicatedin a disease of skeletal muscle—distal arthrogryposis type1 (DA-1). Here we report the first detailed electronmicroscopy studies on human cardiac and skeletal tissuescarrying MyBP-C gene mutations, using samples obtainedfrom HCM and DA-1 patients. We have used establishedimage averaging methods to identify and study the axialdistribution of MyBP-C on the thick filament by averagingprofile plots of the A-band of the sarcomere from electronmicrographs of human cardiac and skeletal myopathyspecimens. Due to the difficulty of obtaining normal humantissue, we compared the distribution to the A-band structurein normal frog skeletal, rat cardiac muscle and incardiac muscle of MyBP-C-deficient mice. Very similaroverall profile averages were obtained from the C-zones incardiac HCM samples and skeletal DA-1 samples withMyBP-C gene mutations, suggesting that mutations inMyBP-C do not
Govindan S, McElligott A, Muthusamy S, et al., 2012, Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 52, Pages: 154-164, ISSN: 0022-2828
Luther PK, Winkler H, Taylor K, et al., 2011, Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 11423-11428, ISSN: 0027-8424
Machuca-Tzili LE, Buxton S, Thorpe A, et al., 2011, Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy, DISEASE MODELS & MECHANISMS, Vol: 4, Pages: 381-392, ISSN: 1754-8403
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.