Myosins
A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.
Myosin Heavy Chains
Myosin Subfragments
Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).
Myosin Light Chains
The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins.
Myocarditis
Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.
Myosin Type II
Myocardium
Ventricular Myosins
Myocytes, Cardiac
Myosin Type V
Actins
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Actomyosin
Cardiomyopathy, Hypertrophic
A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).
Myosin-Light-Chain Kinase
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Nonmuscle Myosin Type IIA
Myosin Type I
Nonmuscle Myosin Type IIB
Adenosine Triphosphatases
Cardiac Output
Heart Ventricles
Autoimmune Diseases
Rabbits
Myofibrils
Actin Cytoskeleton
Carrier Proteins
Cardiomyopathy, Hypertrophic, Familial
Cardiomegaly
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.
Arrhythmias, Cardiac
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Peptide Fragments
Chickens
Death, Sudden, Cardiac
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Molecular Motor Proteins
Cardiomyopathies
A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).
Amino Acid Sequence
Calcium
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Phosphorylation
Protein Isoforms
Cardiomyopathy, Dilated
Myosin Type III
A subclass of myosins originally found in the photoreceptor of DROSOPHILA. The heavy chains can occur as two alternatively spliced isoforms of 132 and 174 KDa. The amino terminal of myosin type III is highly unusual in that it contains a protein kinase domain which may be an important component of the visual process.
Tropomyosin
Troponin I
Adenosine Triphosphate
Troponin
Rheumatic Heart Disease
Heterocyclic Compounds with 4 or More Rings
Propylthiouracil
Adrenergic beta-2 Receptor Antagonists
Protein Binding
Autoantibodies
Swine
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Cardiac Tamponade
Muscle Contraction
Base Sequence
Cardiac Pacing, Artificial
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.
Myosin-Light-Chain Phosphatase
Heart Diseases
Electrophoresis, Polyacrylamide Gel
Disease Models, Animal
Mutation
Hyperthyroidism
Dogs
Echocardiography
Cells, Cultured
Mice, Transgenic
Adenosine Diphosphate
Cross Reactions
Cardiac Catheterization
Ventricular Function, Left
Muscle, Smooth
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
Heart Arrest
Isoenzymes
Binding Sites
Myocardial Infarction
Muscle Proteins
Microscopy, Electron
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Cattle
Hypothyroidism
Enterovirus B, Human
Coxsackievirus Infections
Muscle, Skeletal
Molecular Mimicry
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Thyroxine
The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.
Myoblasts, Cardiac
Dictyostelium
Rats, Sprague-Dawley
Electrocardiography
Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.
Cardiac Imaging Techniques
Rats, Wistar
Turkeys
Organ Specificity
Cardiac Glycosides
Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose.
Autoimmunity
Cyclic AMP-Dependent Protein Kinases
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Cardiac Output, Low
A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.
Gene Expression Regulation
Magnesium
Hemodynamics
Muscle Fibers, Skeletal
Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Out-of-Hospital Cardiac Arrest
Ventricular Remodeling
Gene Expression
Cardiac Volume
rho-Associated Kinases
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
Calmodulin
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
Troponin T
Phenotype
Species Specificity
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Cytoskeleton
Blotting, Western
Heart Defects, Congenital
Mollusca
A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora.
Chemistry
Genes
Chemical Phenomena
Mutation, Missense
Calmodulin-Binding Proteins
Stroke Volume
Cloning, Molecular
Promoter Regions, Genetic
Amoeba
Heart Conduction System
Aging
Cardiac Resynchronization Therapy
Cardiotonic Agents
Cardiopulmonary Resuscitation
The artificial substitution of heart and lung action as indicated for HEART ARREST resulting from electric shock, DROWNING, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation (RESPIRATION, ARTIFICIAL) and closed-chest CARDIAC MASSAGE.
Models, Biological
Ventricular Dysfunction, Left
A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.
Heart Neoplasms
Fetal Heart
Myocardial Ischemia
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).
Connectin
A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.
Acanthamoeba
Models, Cardiovascular
Mice, Inbred Strains
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Treatment Outcome
Fibrosis
Cardiac Electrophysiology
Regulatory Sequences, Nucleic Acid
DNA Primers
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Muscle Development
Point Mutation
Myosin Type IV
Epitope Mapping
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Muscle Fibers, Slow-Twitch
Prospective Studies
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Immunization
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Microfilament Proteins
Pedigree
Hydrogen-Ion Concentration
Muscle Fibers, Fast-Twitch
Microscopy, Fluorescence
Isometric Contraction
Cyanogen Bromide
Cytoplasmic Streaming
Transcription, Genetic
Chick Embryo
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Hypertrophy, Left Ventricular
Isoproterenol
Troponin C
Atrial Natriuretic Factor
Altered cardiac excitation-contraction coupling in mutant mice with familial hypertrophic cardiomyopathy. (1/275)
Excitation-contraction coupling in cardiac muscle of familial hypertrophic cardiomyopathy (FHC) remains poorly understood, despite the fact that the genetic alterations are well defined. We characterized calcium cycling and contractile activation in trabeculae from a mutant mouse model of FHC (Arg403Gln knockin, alpha-myosin heavy chain). Wild-type mice of the same strain and age ( approximately 20 weeks old) served as controls. During twitch contractions, peak intracellular Ca2+ ([Ca2+]i) was higher in mutant muscles than in the wild-type (P < 0.05), but force development was equivalent in the two groups. Ca2+ transient amplitude increased dramatically in both groups as stimulation rate increased from 0.2 to 4 Hz. Nevertheless, developed force fell at the higher stimulation rates in the mutants but not in controls (P < 0.05). The steady-state force-[Ca2+]i relationship was less steep in mutants (Hill coefficient, 2.94 +/- 0.27 vs. 5.28 +/- 0.64; P > 0.003), with no changes in the [Ca2+]i required for 50% activation or maximal Ca2+-activated force. Thus, calcium cycling and myofilament properties are both altered in FHC mutant mice: more Ca2+ is mobilized to generate force, but this does not suffice to maintain contractility at high stimulation rates. (+info)A post-transcriptional compensatory pathway in heterozygous ventricular myosin light chain 2-deficient mice results in lack of gene dosage effect during normal cardiac growth or hypertrophy. (2/275)
Our previous study of homozygous mutants of the ventricular specific isoform of myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L., Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem. 273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle function, we have analyzed heterozygous mutants in depth. Ventricles of heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed normal levels of protein both under basal conditions and following induction of cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited cardiac function comparable to that of wild-type littermate controls both prior to and following aortic constriction. There were no significant differences in contractility and responses to calcium between wild-type and heterozygous unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a molecular nor a physiological cardiac phenotype either at base line or following hypertrophic stimuli. These results suggest that post-transcriptional compensatory mechanisms play a major role in maintaining the level of MLC-2v protein in murine hearts. In addition, as our mlc-2v knockout mutants were created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for ventricular specific gene targeting. (+info)The CACC box and myocyte enhancer factor-2 sites within the myosin light chain 2 slow promoter cooperate in regulating nerve-specific transcription in skeletal muscle. (3/275)
Previous experiments showed that activity of the -800-base pair MLC2slow promoter was 75-fold higher in the innervated soleus (SOL) compared with the noninnervated SOL muscles. Using in vivo DNA injection of MLC2slow promoter-luciferase constructs, the aim of this project was to identify regulatory sites and potential transcription factors important for slow nerve-dependent gene expression. Three sites within the proximal promoter (myocyte enhancer factor-2 (MEF2), E-box, and CACC box) were individually mutated, and the effect on luciferase expression was determined. There was no change in luciferase expression in the SOL and extensor digitorum longus (EDL) muscles when the E-box was mutated. In contrast, the MEF2 mutation resulted in a 30-fold decrease in expression in the innervated SOL muscles (10.3 versus 0.36 normalized relative light units (RLUs)). Transactivation of the MLC2slow promoter by overexpressing MEF2 was only seen in the innervated SOL (676,340 versus 2,225,957 RLUs; p < 0.01) with no effect in noninnervated SOL or EDL muscles. These findings suggest that the active MLC2slow promoter is sensitive to MEF2 levels, but MEF2 levels alone do not determine nerve-dependent expression. Mutation of the CACC box resulted in a significant up-regulation in the EDL muscles (0.23 versus 4.08 normalized RLUs). With the CACC box mutated, overexpression of MEF2 was sufficient to transactivate the MLC2slow promoter in noninnervated SOL muscles (27,536 versus 1, 605,797 RLUs). Results from electrophoretic mobility shift and supershift assays confirm MEF2 protein binding to the MEF2 site and demonstrate specific binding to the CACC sequence. These results suggest a model for nerve-dependent regulation of the MLC2slow promoter in which derepression occurs through the CACC box followed by quantitative expression through enhanced MEF2 activation. (+info)The effect of removing the N-terminal extension of the Drosophila myosin regulatory light chain upon flight ability and the contractile dynamics of indirect flight muscle. (4/275)
The Drosophila myosin regulatory light chain (DMLC2) is homologous to MLC2s of vertebrate organisms, except for the presence of a unique 46-amino acid N-terminal extension. To study the role of the DMLC2 N-terminal extension in Drosophila flight muscle, we constructed a truncated form of the Dmlc2 gene lacking amino acids 2-46 (Dmlc2(Delta2-46)). The mutant gene was expressed in vivo, with no wild-type Dmlc2 gene expression, via P-element-mediated germline transformation. Expression of the truncated DMLC2 rescues the recessive lethality and dominant flightless phenotype of the Dmlc2 null, with no discernible effect on indirect flight muscle (IFM) sarcomere assembly. Homozygous Dmlc2(Delta2-46) flies have reduced IFM dynamic stiffness and elastic modulus at the frequency of maximum power output. The viscous modulus, a measure of the fly's ability to perform oscillatory work, was not significantly affected in Dmlc2(Delta2-46) IFM. In vivo flight performance measurements of Dmlc2(Delta2-46) flies using a visual closed-loop flight arena show deficits in maximum metabolic power (P(*)(CO(2))), mechanical power (P(*)(mech)), and flight force. However, mutant flies were capable of generating flight force levels comparable to body weight, thus enabling them to fly, albeit with diminished performance. The reduction in elastic modulus in Dmlc2(Delta2-46) skinned fibers is consistent with the N-terminal extension being a link between the thick and thin filaments that is parallel to the cross-bridges. Removal of this parallel link causes an unfavorable shift in the resonant properties of the flight system, thus leading to attenuated flight performance. (+info)A fluorescent reporter gene as a marker for ventricular specification in ES-derived cardiac cells. (5/275)
We have established a CGR8 embryonic stem (ES) cell clone (MLC2ECFP) which expresses the enhanced cyan variant of Aequorea victoria green fluorescent protein (ECFP) under the transcriptional control of the ventricular myosin light chain 2 (MLC2v) promoter. Using epifluorescence imaging of vital embryoid bodies (EB) and reverse transcription-polymerase chain reaction (RT-PCR), we found that the MLC2v promoter is switched on as early as day 7 and is accompanied by formation of cell clusters featuring a bright ECFP blue fluorescence. The fluorescent areas within the EBs were all beating on day 8. MLC2ECFP ES cells showed the same time course of cardiac differentiation as mock ES cells as assessed by RT-PCR of genes encoding cardiac-specific transcription factors and contractile proteins. The MLC2v promoter conferred ventricular specificity to ECFP expression within the EB as revealed by MLC2v co-staining of ECFP fluorescent cells. MLC2ECFP-derived cardiac cells still undergo cell division on day 12 after isolation from EBs but withdraw from the cell cycle on day 16. This ES cell clone provides a powerful cell model to study the signalling roads of factors regulating cardiac cell proliferation and terminal differentiation with a view to using them for experimental cell therapy. (+info)Adverse effects of constitutively active alpha(1B)-adrenergic receptors after pressure overload in mouse hearts. (6/275)
Cardiac hypertrophy and function were studied 6 wk after constriction of the thoracic aorta (TAC) in transgenic (TG) mice expressing constitutively active mutant alpha(1B)-adrenergic receptors (ARs) in the heart. Hearts from sham-operated TG animals and nontransgenic littermates (WT) were similar in size, but hearts from TAC/TG mice were larger than those from TAC/WT mice, and atrial natriuretic peptide mRNA expression was also higher. Lung weight was markedly increased in TAC/TG animals, and the incidence of left atrial thrombus formation was significantly higher. Ventricular contractility in anesthetized animals, although it was increased in TAC/WT hearts, was unchanged in TAC/TG hearts, implying cardiac decompensation and progression to failure in TG mice. There was no increase in alpha(1A)-AR mRNA expression in TAC/WT hearts, and expression was significantly reduced in TAC/TG hearts. These findings show that cardiac expression of constitutively actively mutant alpha(1B)-ARs is detrimental in terms of hypertrophy and cardiac function after pressure overload and that increased alpha(1A)-AR mRNA expression is not a feature of the hypertrophic response in this murine model. (+info)The calcineurin-NFAT pathway and muscle fiber-type gene expression. (7/275)
To test for a role of the calcineurin-NFAT (nuclear factor of activated T cells) pathway in the regulation of fiber type-specific gene expression, slow and fast muscle-specific promoters were examined in C2C12 myotubes and in slow and fast muscle in the presence of calcineurin or NFAT2 expression plasmids. Overexpression of active calcineurin in myotubes induced both fast and slow muscle-specific promoters but not non-muscle-specific reporters. Overexpression of NFAT2 in myotubes did not activate muscle-specific promoters, although it strongly activated an NFAT reporter. Thus overexpression of active calcineurin activates transcription of muscle-specific promoters in vitro but likely not via the NFAT2 transcription factor. Slow myosin light chain 2 (MLC2) and fast sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) reporter genes injected into rat soleus (slow) and extensor digitorum longus (EDL) (fast) muscles were not activated by coinjection of activated calcineurin or NFAT2 expression plasmids. However, an NFAT reporter was strongly activated by overexpression of NFAT2 in both muscle types. Calcineurin and NFAT protein expression and binding activity to NFAT oligonucleotides were different in slow vs. fast muscle. Taken together, these results indicate that neither calcineurin nor NFAT appear to have dominant roles in the induction and/or maintenance of slow or fast fiber type in adult skeletal muscle. Furthermore, different pathways may be involved in muscle-specific gene expression in vitro vs. in vivo. (+info)Altered cross-bridge characteristics following haemodynamic overload in rabbit hearts expressing V3 myosin. (8/275)
1. Our goal in this study was to evaluate the effect of haemodynamic overload on cross-bridge (XBr) kinetics in the rabbit heart independently of myosin heavy chain (MHC) isoforms, which are known to modulate kinetics in small mammals. We applied a myothermal-mechanical protocol to isometrically contracting papillary muscles from two rabbit heart populations: (1) surgically induced right ventricular pressure overload (PO), and (2) sustained treatment with propylthiouracil (PTU). Both treatments resulted in a 100 % V3 MHC profile. 2. XBr force-time integral (FTI), evaluated during the peak of the twitch from muscle FTI and tension-dependent heat, was greater in the PO hearts (0.80 +/- 0.10 versus 0.45 +/- 0.05 pN s, means +/- S.E.M., P = 0.01). 3. Within the framework of a two-state XBr model, the PO XBr developed more force while attached (5.8 +/- 0.9 versus 2.7 +/- 0.3 pN), with a lower cycling rate (0.89 +/- 0.10 versus 1.50 +/- 0.14 s(-1)) and duty cycle (0.14 +/- 0.03 versus 0.24 +/- 0.02). 4. Only the ventricular isoforms of myosin light chain 1 and 2 and cardiac troponin I (cTnI) were expressed, with no difference in cTnI phosphorylation between the PO and PTU samples. The troponin T (TnT) isoform compositions in the PO and PTU samples were significantly different (P = 0.001), with TnT2 comprising 2.29 +/- 0.03 % in PO hearts versus 0.98 +/- 0.01 % in PTU hearts of total TnT. 5. This study demonstrates that MHC does not mediate dramatic alterations in XBr function induced by haemodynamic overload. Our findings support the likelihood that differences among other thick and thin filament proteins underlie these XBr alterations. (+info)
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Preventative therapeutic approaches for hypertrophic cardiomyopathy<...
A small-molecule inhibitor of T. gondii motility induces the posttranslational modification of myosin light chain-1 and...
ISMRM 2015) Can quantitative texture analysis on cardiac magnetic resonance differentiate hypertrophic cardiomyopathy patients...
Hypertrophic Cardiomyopathy | JACC: Journal of the American College of Cardiology
Primary heart failure - The Clinical Advisor
C57BL/6 mouse primary heart cells | Creative Bioarray
Frontiers | MYBPC1, an Emerging Myopathic Gene: What We Know and What We Need to Learn | Physiology
What are some of the sub-services you offer | Brookhaven Heart
HCM - Symptoms, Treatments and Resources for HCM
MYL6P3 | 遺伝子情報 | J-GLOBAL 科学技術総合リンクセンター
Abstract P078: Dysregulated Calcium Handling in a Conditional Cardiac Myosin Binding Protein C Knockout Model of Hypertrophic...
Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C | BMC...
An Endogenously Produced Fragment of Cardiac Myosin Binding Protein C is Pathogenic and Can Lead to Heart Failure | Circulation...
Do children with left ventricular noncompaction and a noncompaction-to-compaction ratio | 2 have a better prognosis? | BMC...
Biochemical and Physiological Regulation of Cardiac Myocyte Contraction by Cardiac-Specific Myosin Light Chain Kinase
Left ventricular noncompaction: a 25-year odyssey. by Timothy E. Paterick M.D., J.D., Matt M. Umland et al.
Interstitial 1q43-q43 deletion with left ventricular noncompaction myocardium. - Semantic Scholar
Comparison of Echocardiographic Diagnostic Criteria of Left Ventricular Noncompaction in a Pediatric Population | SpringerLink
Abstract 2160: Myocarditis in Hypertrophic Cardiomyopathy Patients Presenting Acute Clinical Deterioration | Circulation
Elevated carbohydrate antigen 125 levels in hypertrophic cardiomyopathy patients with heart failure | AVESİS
Difference between revisions of 2017 Group Project 3 - Embryology
ISMRM 2017) A comparison of STEAM and spin echo diffusion tensor CMR in hypertrophic cardiomyopathy patients
Clinical and genetic characteristics of hypertrophic cardiomyopathy patients with end-stage disease: A registry-based study. |...
ReP USP - Detalhe do registro: Construction of a regulatory myosin light chain capable regulation of myosin
Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C | BMC Cell...
Five Candidate Genes for Hamster Cardiomyopathy Did not Map to the Cardiomyopathy Locus by FISH Analysis : DNA Research - oi
Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart...
Ebstein anomaly | Norton Childrens Louisville, Ky.
Left ventricular noncompaction 6 AND humans[mesh] AND review[publicati - PubMed - NCBI
Invasive electrophysiology|br|Left ventricular noncompaction: how to identify and treat? A case report | Wita | Kardiologia...
Ovariectomy fails to modify the cardiac myosin isoenzyme profi...
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Isolated ventricular noncompaction syndrome in a nigerian male: case report and review of the literature.
Aspirin guidelines push stroke prevention - The Clinical Advisor
TNNI3K抗体|Abcam中国|Anti-TNNI3K抗体(ab86564)
Blebbistatin
Myosin specificity[edit]. Blebbistatin is a potent inhibitor of nonmuscle myosin IIA and IIB, cardiac myosin, skeletal myosin ... nonmuscle myosin-2 oocyte cytokinesis effective at 300 μM[33] C. elegans nonmuscle myosin-2 acto-myosin colocalization ... for Dictyostelium discoideum myosin II motor domain IC50=2.3 μM, for human β-cardiac myosin subfragment 1 IC50=13 μM,[37] for ... myosin isoform or muscle type assay type IC50 Dictyostelium discoideum myosin II motor domain basal ATPase 2.96 ± 0.45 μM,[7] ...
Neuregulin 1
Downstream effectors of NRG-1/ErbB, include cardiac-specific myosin light chain kinase (cMLCK), Protein Phosphatase type 1 (PP1 ... "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): 2812-24. ... "Identification of cardiac-specific myosin light chain kinase". Circ. Res. 102 (5): 571-80. doi:10.1161/CIRCRESAHA.107.161687. ... Bassani JW, Yuan W, Bers DM (May 1995). "Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac ...
MYLK3
Phosphorylation of cardiac myosin heavy chains (see MYH7B) and light chains (see MYL2) by a kinase, such as MYLK3, potentiates ... 2007). "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): ... "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): 2812-24. ... "Identification of cardiac-specific myosin light chain kinase". Circ. Res. 102 (5): 571-80. doi:10.1161/CIRCRESAHA.107.161687. ...
John M Squire
Atomic model of the human cardiac muscle myosin filament. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):318-323. http://www. ... General model of myosin filament structure. III. Molecular packing arrangements in myosin filaments. J Mol Biol. 1973 Jun 25;77 ... polarity in the myosin filaments of vertebrate smooth muscle, and the proposal of a general packing scheme of myosin molecules ... Probing muscle myosin motor action: X-ray (m3 and m6) interference measurements report motor domain not lever arm movement. J ...
TEAD1
Gupta MP, Gupta M, Dizon E, Zak R (1996). "Sympathetic control of cardiac myosin heavy chain gene expression". Molecular and ... This recruitment leads to the repression of the MLC2v (Myosin Light Chain 2 v) and βMHC ( β-myosin heavy chain ) promoter. ... Regulation of myosin heavy chain genes, cardiac muscular genes troponin T and I Regulation of proliferation, Regulation of ... for positive regulation of cardiac alpha-myosin heavy-chain gene expression". Molecular and Cellular Biology. 17 (7): 3924-36. ...
Deoxyadenosine triphosphate
In cardiac muscle In cardiac myosin, dATP has been shown to be a viable alternative to ATP as an energy substrate for ... June 2019). "Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin". Proceedings of ... In an experiment involving canine dilated cardiomyopathy (DCM), increasing cardiac dATP was found to be a potentially effective ... as well as the rate of cross-bridge of the cardiac muscle of patients in their end-stage congestive heart failure without ...
Richard B. Lanman
"Degradation of canine cardiac myosin and actin by cathepsin D isolated from homologous tissue". Cardiovasc Research. 13 (11): ...
Para-Nitroblebbistatin
"Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels". Frontiers in Physiology. 7: 659. doi:10.3389/fphys ... para-Nitroblebbistatin is a non-phototoxic, photostable myosin inhibitor with low fluorescence. Its myosin inhibitory ... Roman, Bart I.; Verhasselt, Sigrid; Stevens, Christian V. (2018-06-21). "Medicinal Chemistry and Use of Myosin II Inhibitor (S ... Rauscher, Anna Á.; Gyimesi, Máté; Kovács, Mihály; Málnási-Csizmadia, András (July 2018). "Targeting Myosin by Blebbistatin ...
Second-harmonic imaging microscopy
Myosin can also be imaged in skeletal muscle or cardiac muscle. Third-Harmonic Generation (THG) microscopy can be complementary ... SHG also reveals fibroin in silk, myosin in muscles and biosynthetized cellulose. All of this imaging capability can be used to ... Biological materials such as collagen, microtubules, and muscle myosin can produce SHG signals. The SHG pattern is mainly ... "Probing myosin structural conformation in vivo by second-harmonic generation microscopy". Proceedings of the National Academy ...
Troponin I
Cardiac troponin I, TNNI3 (19q13.4, 191044) Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by ... Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes ... Mannu GS, The non-cardiac use and significance of cardiac troponins. Scott Med J, 2014. 59(3): p. 172-8. Tanindi, Asil; Cemri, ... For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more ...
Katarína Horáková
"Peroxidase labelled monoclonal antibody against light chains of human cardiac myosin". General Physiology and Biophysics. 10 (1 ...
Troponin
April 2001). "Cardiac troponin and beta-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis ... No cardiac specific isoforms are known for human TnC. TnC in human cardiac muscle tissue is presented by an isoform typical for ... Gaze DC, Collinson PO; Collinson, PO (December 2005). "Cardiac troponins as biomarkers of drug- and toxin-induced cardiac ... Mannu, GS (August 2014). "The non-cardiac use and significance of cardiac troponins". Scottish Medical Journal. 59 (3): 172-8. ...
UC Davis School of Veterinary Medicine
"A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy". Human Molecular ...
Muscle
Cardiac muscle (myocardium), is also an "involuntary muscle" but is more akin in structure to skeletal muscle, and is found ... The filaments in a sarcomere are composed of actin and myosin. The gross anatomy of a muscle is the most important indicator of ... Cardiac muscle on the other hand, can readily consume any of the three macronutrients (protein, glucose and fat) aerobically ... Cardiac and skeletal muscles are "striated" in that they contain sarcomeres that are packed into highly regular arrangements of ...
Striated muscle tissue
Cardiac muscle lies between the epicardium and the endocardium in the heart. Cardiac muscle fibers generally only contain one ... The calcium drives the movement of myosin and actin filaments. The sarcomere then shortend which causes the muscle to contract ... Unlike skeletal muscle, cardiac muscle cells are unicellular. These cells are connected to each other by intercalated disks, ... Skeletal muscle is able to regenerate far better than cardiac muscle due to satellite cells, which are dormant in all healthy ...
MYLK2
"The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation". ... "Entrez Gene: MYLK2 myosin light chain kinase 2, skeletal muscle". Stull JT, Kamm KE, Vandenboom R (February 2011). "Myosin ... Myosin light chain kinase 2 also known as MYLK2 is an enzyme which in humans is encoded by the MYLK2 gene. This gene encodes a ... Christie JD, Ma SF, Aplenc R (2008). "Variation in the myosin light chain kinase gene is associated with development of acute ...
Omecamtiv mecarbil
Thus due to the unique cardiac myosin activation mechanism, omecamtiv mecarbil could safely improve cardiac function within ... "Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure". Circ Heart Fail. ... "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind ... "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Fail Rev. 14 (4): 289-298. doi:10.1007/ ...
MYLK
2007). "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): ... This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce ... Myosin light chain kinase, smooth muscle also known as kinase-related protein (KRP) or telokin is an enzyme that in humans is ... "Entrez Gene: MYLK myosin, light chain kinase". Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial ...
MiR-208
It also responds to stress and forms part of a hormonal signalling cascade in cardiac cells. A preliminary study has shown a ... miR-208 functions in cardiomyocytes regulating the production of the myosin heavy chain during development. ... miR-208 has been deemed a "myomiR" as it is specifically expressed, or found at much higher levels, in cardiac tissue. Other ... van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN (April 2007). "Control of stress-dependent cardiac growth and ...
Dephosphorylation
April 2012). "Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease ... Dephosphorylation is a key part of the myosin cycling kinetics that directly control the actin-myosin interactions. When the ... particularly the alteration of actin-myosin interactions that are key for providing the underlying force of a heartbeat. ... protein phosphatases are implicated in conditions such as cardiac disease, diabetes, and Alzheimer's disease.[citation needed] ...
Heart
The cardiac output is normalized to body size through body surface area and is called the cardiac index. The average cardiac ... These are mostly associated with muscle contraction, and bind with actin, myosin, tropomyosin, and troponin. They include MYH6 ... the middle cardiac vein (draining the bottom of the left and right ventricles), and small cardiac veins. The anterior cardiac ... and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular ...
Myomesin-2
In cardiac muscle, expression of M-protein continues to increase from neonatal to adult; however, in skeletal muscle, M-protein ... M-protein functions to stabilize the M-line cross-linking titin and myosin; the central portion of M-protein is around the M1- ... Obermann WM, van der Ven PF, Steiner F, Weber K, Fürst DO (Apr 1998). "Mapping of a myosin-binding domain and a regulatory ... Obermann WM, van der Ven PF, Steiner F, Weber K, Fürst DO (Apr 1998). "Mapping of a myosin-binding domain and a regulatory ...
GATA4
Huang WY, Cukerman E, Liew CC (1995). "Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding gene and ... GATA4 promotes cardiac morphogenesis, cardiomyocytes survival, and maintains cardiac function in the adult heart. Mutations or ... "Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene". Mol. Cell. Biol ... 1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". EMBO J. 16 (18): 5687-96. doi:10.1093/emboj/ ...
Lalji Singh
2009). "A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia". Nature ...
Hypertrophic cardiomyopathy
The cardiac myosin binding protein C mutation identified in Maine Coon cats has not been found in any other breed of cat with ... December 2005). "A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy". ... The first genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was discovered in 2005 in Maine ... It fails to acknowledge the age at which relatives suffered sudden cardiac death, as well as the frequency of the cardiac ...
MYL2
"Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in ... Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin ... Loss of cardiac MLCK in mice results in loss of cardiac MLC-2v phosphorylation and cardiac abnormalities. Mutations in MYL2 ... Ventricular myosin light chain-2 (MLC-2v) refers to the ventricular cardiac muscle form of myosin light chain 2 (Myl2). MLC-2v ...
Bernhard Brenner
... he started to study mutations in cardiac myosin related to hypertrophic cardiomyopathy. He died in 2017, from cancer. Yu, L.C ...
Karen Wonders
Effects on Running Activity and Cardiac Myosin Heavy Chain". "Endurance exercise training preserves cardiac function in rats ... effects on running activity and cardiac myosin heavy chain. Anticancer research, 29(11), 4401-4407. Wonders, K. Y., Hydock, D. ... Wonders published a paper in 2008 discussing the impacts of a single bout of acute endurance exercise in terms of the cardiac ... She found out that the acute exercise bout performed 24 hours prior to the DOX treatment protected against cardiac dysfunction ...
Concussions in sport
"Radioactive labeling and location of specific thiol groups in myosin from fast, slow and cardiac muscles". Biochimica et ... "Preparation and characterization of an enzymatically active immobilized derivative of myosin". Biochimica et Biophysica Acta ( ...
ROCK1
Cardiac troponin is another ROCK1 substrate that upon phosphorylation causes reduction in tension in cardiac myocytes. ROCK1 ... It is a key regulator of actin-myosin contraction, stability, and cell polarity. These contribute to many progresses such as ... ROCK1 activation by RhoA also promotes stabilization of F-actin, phosphorylation of regulatory myosin light chain (MLC) and an ... Activated ROCK1 phosphorylates MLC involved in actin-myosin contractility. RhoA also activates focal adhesion kinase activity. ...
Pleiotropy
... of known causes of death in diagnosed patients relating to cardiovascular complications and congestive cardiac failure. Other ... in an intron of the Myosin heavy polypeptide 4 gene.[38] ... "A novel intronic single nucleotide polymorphism in the myosin ...
Muscle spindle
Primary type Ia sensory fibers (large diameter) spiral around all intrafusal muscle fibres, ending near the middle of each fibre. Secondary type II sensory fibers (medium diameter) end adjacent to the central regions of the static bag and chain fibres.[2] These fibres send information by stretch-sensitive mechanically-gated ion-channels of the axons.[3] The motor part of the spindle is provided by motor neurons: up to a dozen gamma motor neurons and one or two beta motor neurons, collectively called fusimotor neurons.[citation needed] These activate the muscle fibres within the spindle. Gamma motor neurons supply only muscle fibres within the spindle, whereas beta motor neurons supply muscle fibres both within and outside of the spindle. Activation of the neurons causes a contraction and stiffening of the end parts of the muscle spindle muscle fibers. Fusimotor neurons are classified as static or dynamic according to the type of muscle fibers they innervate and their effects on the responses of ...
Eccentric training
Eccentric contractions and cardiac output: With lower cost of oxygen how would eccentric exercise affect the heart? A study was ... When in a concentric exercise, shortening of a muscle occurs as the myosin and actin cross bridges repeatedly attach and detach ... The unique trait of greater overloads to the muscle with less strenuous impact on the body, as well as cardiac and respiratory ... Add to these factors disease and cardiac and respiratory illness. Eccentric training enables the elderly, and those with the ...
Tumor necrosis factor alpha
negative regulation of myosin-light-chain-phosphatase activity. • negative regulation of transcription, DNA-templated. • ... cardiac myocytes, adipose tissue, fibroblasts, and neurons.[5] Large amounts of TNF are released in response to ...
Muscle - Simple English Wikipedia, the free encyclopedia
The cardiac muscle is not voluntary. The smooth muscles are the other muscles in the body that are involuntary. Smooth muscles ... Muscle cells are filled with proteins called actin and myosin. These are the proteins that make the muscle contract (get ... The cardiac muscle is the muscle in the heart. When this muscle contracts it pushes blood through the circulatory system. ... This calcium sticks to the specialized proteins actin and myosin. This triggers these proteins to contract the muscle. ...
Muscle
Cardiac muscle fibers are interconnected by intercalated discs,[12] giving that tissue the appearance of a syncytium. ... Muscle cells contain protein filaments of actin and myosin that slide past one another, producing a contraction that changes ... Cardiac muscle (myocardium), is also an "involuntary muscle" but is more akin in structure to skeletal muscle, and is found ... Cardiac and skeletal muscles are "striated" in that they contain sarcomeres that are packed into highly regular arrangements of ...
DLG1
regulation of ventricular cardiac muscle cell action potential. • regulation of potassium ion import. • regulation of voltage- ... Wu H, Nash JE, Zamorano P, Garner CC (Aug 2002). "Interaction of SAP97 with minus-end-directed actin motor myosin VI. ... There is also a myosin VI binding site near n-terminal which may be involved in the internalization of AMPAR.[12][13] ... gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. • regulation of ...
Limb-girdle muscular dystrophy
Electrocardiography (cardiac arrhythmias in LGMD1B can occur). Types[edit]. The "LGMD1" family is autosomal dominant, and the " ... Myosin. *Elejalde syndrome. *Hypertrophic cardiomyopathy 1, 8, 10. *Usher syndrome 1B. *Freeman-Sheldon syndrome ... An audio clip recording of a PVC symptom, made with a cardiac event monitor. ...
Adenosine receptor
However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by ... phosphorylate myosin light chain → myosin light chain plus actin → bronchoconstriction[citation needed] ... Osadchii OE (June 2007). "Myocardial phosphodiesterases and regulation of cardiac contractility in health and cardiac disease ... Also recently discovered A2B has Gq → DAG and IP3 → Release calcium → activate calmodulin → activate myosin light chain kinase ...
Atrial fibrillation
... involved in the regulation of cardiac conduction, modulation of ion channels and in cardiac development. Have been also ... This is typically due to sarcoidosis but may also be due to autoimmune disorders that create autoantibodies against myosin ... Due to inadequate cardiac output, individuals with AF may also complain of light-headedness,[23] may feel like they are about ... Cardiac glycosides (e.g., digoxin) - have less use, apart from in older people who are sedentary. They are not as effective as ...
Perimysium
... is a sheath of connective tissue that groups muscle fibers into bundles (anywhere between 10 and 100 or more) or fascicles. Studies of muscle physiology suggest that the perimysium plays a role in transmitting lateral contractile movements. This hypothesis is strongly supported in one exhibition of the existence of "perimysial junctional plates" in ungulate flexor carpi radialis muscles constructed by Emilie Passerieux.[1] The overall comprehensive organization of the perimysium collagen network, as well as its continuity and disparateness, however, have still not been observed and described thoroughly everywhere within the muscle. Found to have type I, III, VI, and XII collagen. ...
Myofilament
... such as skeletal and cardiac muscle, the actin and myosin filaments each have a specific and constant length in the order of a ... Each thick filament is approximately 15 nm in diameter, and each is made of several hundred molecules of myosin. A myosin ... The filaments of actin and myosin then form linkages. After binding, myosin pulls actin filaments toward each other, or inward ... Half of the myosin heads angle to the left and half of them angle to the right, creating an area in the middle of the filament ...
Esophagus
... and esophageal cardiac glands, similar to cardiac glands of the stomach, located in the lamina propria and most frequent in the ... "Adult human upper esophageal sphincter contains specialized muscle fibers expressing unusual myosin heavy chain isoforms". J. ... A muscular ring, called the cardiac sphincter, connects the stomach to the esophagus. This sphincter is very well developed in ... It is also called the cardiac sphincter or cardioesophageal sphincter, named from the adjacent part of the stomach, the cardia ...
Tissue transglutaminase
... tTG shows promise as a potential therapeutic target to treat cardiac fibrosis, through the activity of a highly selective tTG ... Evidence shows that intracellular tTG crosslinks itself to myosin. It is also believed that tTG may stabilize the structure of ... "Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor" ... is thought to be involved in the regulation of the cytoskeleton by crosslinking various cytoskeletal proteins including myosin ...
Nitric oxide synthase
nNOS in the heart protects against cardiac arrhythmia induced by myocardial infarction. The primary receiver for NO produced by ... the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation. eNOS plays a critical role in ... nNOS has many other physiological functions, including regulation of cardiac function and peristalsis and sexual arousal in ... is involved in regulation of cardiac function and angiogenesis (growth of new blood vessels). NO produced by eNOS has been ...
Maine coon
NLM (2019) MYBPC3 gene (myosin binding protein C, cardiac). National Library of Medicine (US). Genetics Home Reference, 2019. ...
CDC42
cardiac conduction system development. • positive regulation of protein phosphorylation. • negative regulation of epidermal ...
MYH9
"Ablation of nonmuscle myosin II-B and II-C reveals a role for nonmuscle myosin II in cardiac myocyte karyokinesis". Molecular ... Myosin-9 also known as myosin, heavy chain 9, non-muscle or non-muscle myosin heavy chain IIa (NMMHC-IIA) is a protein which in ... myosin II filament. • cell cortex. • brush border. • actomyosin. • myosin complex. • integrin complex. • ruffle. • cell nucleus ... Myosin IIs are motor proteins that are part of a superfamily composed of more than 30 classes.[7][8][9] Class II myosins ...
Intrafusal muscle fiber
... s are skeletal muscle fibers that serve as specialized sensory organs (proprioceptors) that detect the amount and rate of change in length of a muscle.[1] They constitute the muscle spindle and are innervated by both sensory (afferent) and motor (efferent) fibers. Gamma efferents from small multipolar cells from anterior gray column innervate it. These form a part of neuromuscular spindles. Intrafusal muscle fibers are walled off from the rest of the muscle by an outer connective tissue sheath consisting of flattened fibroblasts and collagen.[2] This sheath has a spindle or "fusiform" shape, hence the name "intrafusal". There are two types of intrafusal muscle fibers: nuclear bag and nuclear chain fibers. They bear two types of sensory ending, known as annulospiral and flower-spray endings. Both ends of these fibers contract but the central region only stretches and does not contract. They are innervated by gamma motor neurons and beta motor neurons. It is by the sensory ...
TLN1
"Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 7 July 2015.. *^ Hamada K, Shimizu T, Matsui T, Tsukita S, ... Belkin AM, Zhidkova NI, Koteliansky VE (May 1986). "Localization of talin in skeletal and cardiac muscles". FEBS Letters. 200 ( ... These data suggest that upregulation of talin-1 in cardiac hypertrophy may be detrimental to cardiomyocytes function.[39] ... to integrins and localized to intercalated discs of cardiac muscle and to costamere structures of both skeletal and cardiac ...
Protein kinase A
myocyte (cardiac muscle). cardiovascular. *norepinephrine → β-adrenergic receptor. *sequester Ca2+ in sarcoplasmic reticulum * ... Contributes to vasodilation (phosphorylates, and thereby inactivates, Myosin light-chain kinase) hepatocyte. liver. * ... In cardiac muscleEdit. In a cascade mediated by a GPCR known as β1 adrenoceptor, activated by catecholamines (notably ... Rodriguez P, Kranias EG (December 2005). "Phospholamban: a key determinant of cardiac function and dysfunction". Archives des ...
Strength training
Muscle tone or firmness is derived from the increase in actin and myosin cross filaments in the sarcomere. When this occurs the ... Central catheter monitoring during resistance training reveals increased cardiac output, suggesting that strength training ... and improved cardiac function. Training commonly uses the technique of progressively increasing the force output of the muscle ... Low volume strength training of 5 repetitions or fewer will increase strength by increasing actin and myosin cross filaments ...
HIV associated cardiomyopathy
Cardiac autoimmunity in HIV related heart muscle disease. Heart 1998;79:599-604. Lipshultz SE, Easley KA, Orav EJ, et al. ... anti-α-myosin autoantibodies) than HIV-infected patients with healthy hearts and HIV-negative controls. In addition, patients ... Nutritional status and cardiac mass and function in children infected with the human immunodeficiency virus. Am J Clin Nutr ... Cardiac dysfunction in the HIV-1 transgenic mouse treated with zidovudine. Lab Invest 2000;80:187-97. Lewis W, Simpson JF, ...
Prostacyclin receptor
For example, the IP agonist iloprost is contraindicated in patients with unstable angina; decompensated cardiac failure (unless ... calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/Calcineurin/Nuclear factor ... Furthermore, IP(-/-) mice on a high salt diet develop significantly higher levels of hypertension, cardiac fibrosis, and ... "A Comparison of Inhaled Nitric Oxide Versus Inhaled Epoprostenol for Acute Pulmonary Hypertension Following Cardiac Surgery". ...
Myocyte
A = A-band, region of myosin. I = I-band, region of just actin. H = H-zone, region of just myosin. Z = Z-line, sarcomere ... cardiac, skeletal, and smooth muscle cells. The striated cells of cardiac and skeletal muscles are referred to as muscle fibers ... Two commonly confused methods are histochemical staining for myosin ATPase activity and immunohistochemical staining for Myosin ... In cardiac myocytes this forms a scalloped surface.[10]. The cytoskeleton is what the rest of the cell builds off of and has ...
Congenital heart defect
A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, α-myosin heavy chain ( ... Non-cardiac manifestations[19]. Upper limb abnormalities. Small or absent thymus Small or absent parathyroids Facial ... Niessen, K.; Karsan, A. (2008). "Notch Signaling in Cardiac Development". Circulation Research. 102 (10): 1169-1181. doi: ... Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4 forms a ...
Physiological cross-sectional area
The other component, orthogonal to the direction of action of the muscle (Orthogonal force = Total force × sinΦ) is not exerted on the tendon, but simply squeezes the muscle, by pulling its aponeuroses toward each other. Notice that, although it is practically convenient to compute PCSA based on volume or mass and fiber length, PCSA (and therefore the total fiber force, which is proportional to PCSA) is not proportional to muscle mass or fiber length alone. Namely, the maximum (tetanic) force of a muscle fiber simply depends on its thickness (cross-section area) and type. By no means it depends on its mass or length alone. For instance, when muscle mass increases due to physical development during childhood, this may be only due to an increase in length of the muscle fibers, with no change in fiber thickness (PCSA) or fiber type. In this case, an increase in mass does not produce an increase in force. Sometimes, the increase in mass is associated with an increase in thickness. Only in this ...
T-tubule
In cardiac muscle cells, as the action potential passes down the T-tubules it activates L-type calcium channels in the T- ... In skeletal muscle cells, T-tubules are between 20 and 40 nm in diameter and are typically located either side of the myosin ... T-tubules (transverse tubules) are extensions of the cell membrane that penetrate into the centre of skeletal and cardiac ... Chemicals such as glycerol[16] or formamide[12] (for skeletal and cardiac muscle respectively) can be added to the ...
Equine anatomy
Muscle fibers have myofibrils, which are able to contract due to actin and myosin. A muscle together with its tendon and bony ... A muscular ring, called the cardiac sphincter, connects the stomach to the esophagus. This sphincter is very well developed in ...
Voltage-gated calcium channel
The activated calmodulin molecule activates myosin light-chain kinase (MLCK), which phosphorylates the myosin in thick ... In cardiac muscle, opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the ... Phosphorylated myosin is able to form crossbridges with actin thin filaments, and the smooth muscle fiber (i.e., cell) ... The β subunit has effects on the kinetics of the cardiac α1C in Xenopus laevis oocytes co-expressed with β subunits. The β ...
Myosin binding protein C, cardiac - Wikipedia
"Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain ... "Protein Information - Myosin-binding protein C, cardiac-type". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). NHLBI ... "Double heterozygosity for mutations in the beta-myosin heavy chain and in the cardiac myosin binding protein C genes in a ... "A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in ...
Myosin-binding protein C, cardiac-type (Q14896) | InterPro | EMBL-EBI
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Cytokinetics Announces Fundamental Research In Cardiac Myosin Activation In The Journal Science - Redorbit
The publication titled, "Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure," discusses the ... Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of ... The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart ... Cytokinetics Announces Fundamental Research In Cardiac Myosin Activation In The Journal Science. by Sam Savage ...
Cytokinetics Announces Initiation of Phase 1 Clinical Trial of CK-3773274, a Cardiac Myosin Inhibitor
CK-274 is a novel cardiac myosin inhibitor, discovered ... CK-274 is a novel cardiac myosin inhibitor, discovered by ... CK-274 reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial ... CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its ... Cytokinetics is also developing CK-274, a novel cardiac myosin inhibitor that company scientists discovered independent of its ...
JCI -
A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart
... cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well ... Cardiac-specific myosin regulatory light chain is a specific substrate of cardiac-MLCK. Because this protein kinase contained a ... In mice, however, targeted deletion of the cardiac ventricular myosin light chain, a specific substrate of cardiac-MLCK, was ... mRNA expression of ANP and β myosin heavy chain, representative markers of cardiac hypertrophy, were also unaffected by cardiac ...
Recombinant Human beta-cardiac myosin heavy chain protein (ab112326) | Abcam
Recombinant Human beta-cardiac myosin heavy chain protein is a Wheat germ Protein fragment 1 to 109 aa range and validated in ... Cardiac MHC exists as two isoforms in humans, alpha-cardiac MHC and beta-cardiac MHC. These two isoforms are expressed in ... Protein - Recombinant Human beta-cardiac myosin heavy chain protein (ab112326) ELISA, WB, SDS-PAGE ... Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 ...
Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic...
Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ...
MYLK2 - Myosin light chain kinase 2, skeletal/cardiac muscle - Capra hircus (Goat) - MYLK2 gene & protein
Myosin light chain kinase 2, skeletal/cardiac muscleARBA annotation. Automatic assertion according to rulesi ... tr,A0A452EYU2,A0A452EYU2_CAPHI Myosin light chain kinase 2, skeletal/cardiac muscle OS=Capra hircus OX=9925 GN=MYLK2 PE=3 SV=1 ... L-seryl-[myosin light chain]*Search proteins in UniProtKB for this molecule. ... L-seryl-[myosin light chain]*Search proteins in UniProtKB for this molecule. ...
Determination of the critical residues responsible for cardiac myosin binding protein C's interactions.
Despite early demonstrations of myosin binding protein Cs (MyBP-C) interaction with actin, different investigators have ... Myocytes, Cardiac / metabolism*. Myosin Subfragments / chemistry, metabolism. Protein Binding / genetics. Protein Interaction ... 0/Actins; 0/Carrier Proteins; 0/Myosin Subfragments; 0/myosin-binding protein C ... Despite early demonstrations of myosin binding protein Cs (MyBP-C) interaction with actin, different investigators have ...
Phophoproteome Characterization of Cardiac Myosin Binding Protein-C
Phosphoproteome Characterization of Cardiac Myosin Binding Protein-C. By Emily Humphreys 10.30.2013 Cardiac myosin binding ... Accelerating ScienceAccelerating Proteomics / Cardiovascular / Phosphoproteome Characterization of Cardiac Myosin Binding ... 2013, July) "Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts," ... 1. James, J., and Robbins, J. (2011) "Signaling and myosin-binding protein C," The Journal of Biological Chemistry, 286(12) (pp ...
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to...
Human β-cardiac myosin structural models. (A) PyMol homology model of human β-cardiac myosin S1 in the prestroke state showing ... The Cardiac Myosin Inhibitor Mavacamten Stabilizes the SRX Folded-Back State of Purified Human β-Cardiac Myosin.. Using the ... The Cardiac Myosin Inhibitor Mavacamten Stabilizes an SRX Folded State of Porcine and Human Cardiac Muscle Fibers.. To examine ... 2017) A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle. J Biol Chem 292 ...
Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light...
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to...
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ...
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and...
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ...
Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in...
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to ... Journal Article: Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic ... Title: Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic ... Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were ...
COMPARATIVE STUDIES OF LIGHT MEROMYOSIN PARACRYSTALS DERIVED FROM RED, WHITE, AND CARDIAC MUSCLE MYOSINS | JCB
COMPARATIVE STUDIES OF LIGHT MEROMYOSIN PARACRYSTALS DERIVED FROM RED, WHITE, AND CARDIAC MUSCLE MYOSINS. A. Nakamura, F. ... COMPARATIVE STUDIES OF LIGHT MEROMYOSIN PARACRYSTALS DERIVED FROM RED, WHITE, AND CARDIAC MUSCLE MYOSINS ... Tryptic and chymotryptic light meromyosin paracrystals from red and cardiac muscles of rabbit show a negative and positive ... The results are discussed in terms of the molecular structure and the functional properties of various myosins. ...
Myosin-based contraction is not necessary for cardiac c-looping in the chick embryo | SpringerLink
During the initial phase of cardiac looping, known as c-looping, the heart bends and twists into a c-shaped tube with the ... Myosin-based contraction is not necessary for cardiac c-looping in the chick embryo. ... Primitive cardiac cavities vs. primitive cardiac segments. In: de la Cruz MV, Markwald RR (eds) Living morphogenesis of the ... Harvey RP (1998) Cardiac looping-an uneasy deal with laterality. Semin Cell Dev Biol 9:101-108PubMedCrossRefGoogle Scholar ...
Myosin Heavy Chain 6, Cardiac Muscle, alpha (MYH6) ELISA Kits
Myosin heavy chain, cardiac muscle alpha isoform (MyHC-alpha) , alpha cardiac MHC , alpha myosin , cardiac myosin heavy chain ... cardiac muscle, alpha , myosin, heavy polypeptide 6, cardiac muscle, alpha , myosin-6 , myosin, heavy polypeptide 6, cardiac ... myHC-alpha , myosin heavy chain 6 , myosin heavy chain polypeptide 6 cardiac muscle adult , myosin heavy chain, cardiac muscle ... Myosin Heavy Chain 6, Cardiac Muscle, alpha (MYH6) ELISA Kits. Cardiac muscle myosin is a hexamer consisting of two heavy chain ...
Myosin Heavy Chain 7, Cardiac Muscle, beta (MYH7) ELISA Kits
... cardiac myosin heavy chain beta , beta cardiac myosin heavy chain , myosin 7 , myosin heavy chain slow type 1 (beta cardiac) , ... myosin heavy chain (AA 1-96) , myosin heavy chain 7 , myosin heavy chain slow isoform , myosin heavy chain, cardiac muscle beta ... beta myosin heavy chain , myHC-slow , myosin heavy chain polypeptide 7 cardiac muscle fetal , myosin heavy chain, cardiac ... myosin, heavy chain 7, cardiac muscle, beta (MYH7) Antikörper * myosin, heavy polypeptide 7, cardiac muscle, beta (Myh7) ...
Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime (Journal...
Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime ... title = {Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime},. ... "Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime". United ... Title: Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime. ...
Swimming causes myosin adaptations in the rat cardiac isograft. | Circulation Research
Swimming causes myosin adaptations in the rat cardiac isograft.. S V Advani, D Geenen, A Malhotra, S M Factor, J Scheuer ... The cardiac isograft was also associated with a decrease in the percent of V1 myosin isoenzyme, which was attenuated by ... The cardiac isograft exhibited atrophy (32-35%), which was not attenuated by swimming. ... To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, ...
Inotropic interventions do not change the resting state of myosin motors during cardiac diastole
... myosin motors are packed in helical tracks on the surface of the thick filament, folded toward the center of the sarcomere, and ... skeletal and cardiac) muscle is in its relaxed state, ... do not change the resting state of myosin motors during cardiac ... When striated (skeletal and cardiac) muscle is in its relaxed state, myosin motors are packed in helical tracks on the surface ... Thick filament mechanosensing has been proposed as the mechanism by which myosin motors in cardiac muscle become available to ...
Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human β-cardiac myosin | Journal of...
... which is highly conserved among the cardiac myosins, from mouse α-cardiac to human β-cardiac myosin (Spudich, 2015). The mesa ... Human cardiomyopathy mutations are a leading cause of cardiac death. The human β-cardiac myosin motor is a major site in the ... 2011). Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck? J. ... 2014). The hypertrophic cardiomyopathy myosin mutation R453C alters ATP binding and hydrolysis of human cardiac beta-myosin. J ...
Myosin isoenzyme changes in several models of rat cardiac hypertrophy. | Circulation Research
Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... We studied the effect of chronic mechanical overloading on the isoenzyme composition of rat cardiac myosin in several ...
Myosin binding protein C, cardiac (MYBPC3) - 623 nt intron 02 reference sequence
PRIME PubMed | [Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods...
Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods of hibernation ... TY - JOUR T1 - [Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods ... Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods of hibernation]. ... Myosin Light Chains of Skeletal and Cardiac Muscles of Ground Squirrel Citillus Undulatus in Different Periods of Hibernation ...
Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and...
Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and ... Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and ... Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and ... Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and ...
Cardiac myosin-binding protein C is a novel marker of myocardial injury and fibrosis in aortic stenosis | Heart
Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy | Science...
Development of human β-cardiac myosin protein models. We developed our models on the basis of known human β-cardiac myosin S1 ... by using human β-cardiac myosin. Recent studies using human β-cardiac myosin carrying the R453C mutation (10) or the R403Q ... 5 shows the tarantula skeletal myosin structure of Alamo et al. (49), which we homology-modeled to the human β-cardiac myosin ... Myosin constructs and protein expression. Human β-cardiac myosin S1s with three converter domain mutations (R719W, R723G, and ...
Myosin S1 Fragment (Cardiac) from Cytoskeleton, Inc.
Cardiac myosin protein (S1 fragment) purified from bovine heart tissue and biologically active. View protocol, results, and ... Cardiac myosin protein has been purified from bovine heart tissue(1, 2). The full length myosin protein was purified with its ... A 20 μg sample of full length bovine cardiac myosin protein (lane A) and the corresponding S1 myosin (lane B) were separated by ... The biological activity of bovine cardiac myosin S1 fragment can be determined from its rate of F-actin activated ATP ...
ProteinIsoformHypertrophicContractilitySarcomereContractionGeneATPaseChainsAbstractProteinsMyocytesIsoformsMYH7TroponinActivatorMutationHypertrophyCardiomyopathyBeta-cardiacFilamentsRecombinant HumanGenesInteractionMolecularMoleculeNovel cardiacFunction of myosinPhosphorylation of cardiac myosinMyocardialKineticsAntibodiesSkeletal and cardiacMyopathyHumanAdultLightFast skeletal muscleElectrophoresisRegulationThickTightly bound to actinOmecamtiv MecarbilHeart failureMutations in patientsSmooth muscle myosin
Protein91
- The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. (wikipedia.org)
- cMyBP-C is a myosin-associated protein that binds at 43 nm intervals along the myosin thick filament backbone, stretching for 200 nm on either side of the M-line within the crossbridge-bearing zone (C-region) of the A band in striated muscle. (wikipedia.org)
- In its dephosphorylated state, cMyBP-C binds predominantly to myosin S2 and brakes crossbridge formation, however, when phosphorylated in response to β-adrenergic stimulation through activating cAMP-dependent protein kinase (PKA), it favours binding to actin, then accelerating crossbridge formation, enhancing force development and promoting relaxation. (wikipedia.org)
- Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2). (abcam.com)
- Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic Stimulation. (nih.gov)
- Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. (nih.gov)
- Phosphorylation and function of cardiac myosin binding protein-C in health and disease. (nih.gov)
- During the past 5 years there has been an increasing body of literature describing the roles cardiac myosin binding protein C (cMyBP-C) phosphorylation play in regulating cardiac function and heart failure. (nih.gov)
- cMyBP-C is a sarcomeric thick filament protein that interacts with titin, myosin and actin to regulate sarcomeric assembly, structure and function. (nih.gov)
- Determination of the critical residues responsible for cardiac myosin binding protein C's interactions. (biomedsearch.com)
- Despite early demonstrations of myosin binding protein C's (MyBP-C) interaction with actin, different investigators have reached different conclusions regarding the relevant and necessary domains mediating this binding. (biomedsearch.com)
- Cardiac myosin binding protein-C (cMyBP-C) is important in heart contractions. (thermofisher.com)
- 1. James, J., and Robbins, J. (2011) " Signaling and myosin-binding protein C ," The Journal of Biological Chemistry, 286(12) (pp. 9913 - 19). (thermofisher.com)
- 2013, July) " Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts ," Journal of Molecular and Cellular Cardiology, 60 (pp. 116 - 20). (thermofisher.com)
- Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. (ahajournals.org)
- Additionally we are shipping Myosin Heavy Chain 6, Cardiac Muscle, alpha Antibodies (44) and Myosin Heavy Chain 6, Cardiac Muscle, alpha Proteins (10) and many more products for this protein. (antibodies-online.com)
- Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. (antikoerper-online.de)
- Zusätzlich bieten wir Ihnen Myosin Heavy Chain 7, Cardiac Muscle, beta Antikörper (70) und Myosin Heavy Chain 7, Cardiac Muscle, beta Proteine (8) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
- During diastole, none of the signals related to the OFF state of the thick filament are significantly affected by these interventions, except the intensity of both myosin-binding protein C- and troponin-related meridional reflections, which reduce by 20% in the presence of isoprenaline. (ovid.com)
- The gain of this positive feedback may be modulated by both sarcomere length and the degree of phosphorylation of myosin-binding protein C. Thick filament mechanosensing has been proposed as the mechanism by which myosin motors in cardiac muscle become available to bind actin. (ovid.com)
- Both are caused by mutations in the genes encoding the fundamental force-generating protein machinery of the cardiac muscle sarcomere, including human β-cardiac myosin, the motor protein that powers ventricular contraction. (biologists.org)
- Our studies are extending beyond myosin interactions with pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin, the roles of regulatory light chain phosphorylation on the functions of the system, and the possible roles of myosin binding protein-C and titin, important regulatory components of both cardiac and skeletal muscles. (biologists.org)
- We therefore examined the reversible acetylation of the A-band protein, myosin heavy chains (MHCs). (ahajournals.org)
- Future work includes how these mutations affect protein interactions within the sarcomere that increase the availability of myosin heads participating in force production. (sciencemag.org)
- 3 ) reported a missense mutation, R403Q, in the β-cardiac myosin heavy chain gene (MYH7) in a cohort of HCM patients, and since then, hundreds of different mutations in not only myosin but also other sarcomeric proteins [for example, myosin binding protein-C (MyBP-C), troponin I, and cardiac actin] have been identified. (sciencemag.org)
- Cardiac myosin protein has been purified from bovine heart tissue(1, 2). (cytoskeleton.com)
- The full length myosin protein was purified with its essential light chains (ELC) and regulatory light chains (RLC), see Figure 1and 2. (cytoskeleton.com)
- Bovine cardiac myosin S1 fragment protein is supplied as a white lyophilized powder. (cytoskeleton.com)
- Legend: Myosin is a hexameric protein consisting of two heavy chains and two light chains. (cytoskeleton.com)
- A 20 μg sample of full length bovine cardiac myosin protein (lane A) and the corresponding S1 myosin (lane B) were separated by electrophoresis using a 4-20% SDS-PAGE gel and stained with Coomassie Blue.The arrow indicates the myosin heavy chain (approx. (cytoskeleton.com)
- It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. (portlandpress.com)
- Background- Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. (unl.edu)
- Cytokinetics' cardiovascular disease program is focused to cardiac myosin, a motor protein essential to cardiac muscle contraction. (marketwired.com)
- Background Variants in the cardiac myosin-binding protein C gene ( MYBPC3 ) are a common cause of hypertrophic cardiomyopathy (HCM) in adults and have been associated with late-onset disease, but there are limited data on their role in paediatric-onset HCM. (bmj.com)
- The mRNAs of known downstream targets of GATA4 during secondary cardiac field development, the cardiogenic factors Hand1, Hand2 and Nkx-2.5, are also decreased, consistent with the reduced GATA4 protein accumulation. (biologists.org)
- The gain of this positive feedback may be modulated by both sarcomere length and the degree of phosphorylation of myosin-binding protein C. (rupress.org)
- Testing of the cell‐permeant peptide inhibitor MMI‐0100 efficacy in ameliorating cardiac fibrosis in a well‐defined model of sarcomere protein caused cardiac disease. (ahajournals.org)
- Cardiac myosin-binding protein C in hypertrophic cardiomyopathy: mechanisms and therapeutic opportunities. (semanticscholar.org)
- Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filaments of the sarcomere. (semanticscholar.org)
- The Role of Cardiac Myosin Binding Protein C3 in Hypertrophic Cardiomyopathy-Progress and Novel Therapeutic Opportunities. (semanticscholar.org)
- Localization of the binding site of the C-terminal domain of cardiac myosin-binding protein-C on the myosin rod. (ox.ac.uk)
- cMyBP-C [cardiac (MyBP-C) myosin-binding protein-C)] is a sarcomeric protein involved both in thick filament structure and in the regulation of contractility. (ox.ac.uk)
- A novel approach to improve cardiac LV systolic function that may address these limitations is through activation of the force-generating protein itself, cardiac myosin. (ahajournals.org)
- Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain C2. (semanticscholar.org)
- Myosin-binding protein C (MyBP-C) binds to myosin with two binding sites, one close to the N terminus and the other at the C terminus. (semanticscholar.org)
- Normal cardiac contraction in mice lacking the proline-alanine rich region and C1 domain of cardiac myosin binding protein C. (semanticscholar.org)
- Orientation of myosin binding protein C in the cardiac muscle sarcomere determined by domain-specific immuno-EM. (semanticscholar.org)
- Should the Rat Myosin Binding Protein C, Cardiac (MYBPC3) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. (glideruniversity.org)
- Description: A sandwich quantitative ELISA assay kit for detection of Rat Myosin Binding Protein C, Cardiac (MYBPC3) in samples from serum, plasma or other biological fluids. (glideruniversity.org)
- Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Myosin Binding Protein C, Cardiac (MYBPC3) in serum, plasma, tissue homogenates and other biological fluids. (glideruniversity.org)
- Known also as Myosin Binding Protein C, Cardiac elisa. (glideruniversity.org)
- MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. (mybiosource.com)
- Regulatory phosphorylation of the cardiac isoform in vivo by cAMP-dependent protein kinase (PKA) upon adrenergic stimulation may be linked to modulation of cardiac contraction. (mybiosource.com)
- Mutations in the MYBPC3 gene encoding human cardiac myosin-binding protein-C (cMyBP-C) are associated with familial hypertrophic cardiomyopathy (FHC), but the molecular mechanisms involved are not fully understood. (oup.com)
- Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. (elsevier.com)
- Interaction analyses elucidate the pathophysiology of HCM-causing missense mutations in cardiac myosin binding protein-C. (ox.ac.uk)
- Myosin Binding Protein C, Cardiac (MYBPC3)- Cloud-Clone Corp. (cloud-clone.com)
- Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction? (cloud-clone.com)
- Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. (cloud-clone.com)
- Cardiac myosin binding protein-C (cMyBP-C) is a member of the immunoglobulin (Ig) superfamily of proteins and consists of 8 Ig- and 3 fibronectin III (FNIII)-like domains along with a unique regulatory sequence referred to as the MyBP-C motif or M-domain. (elsevier.com)
- Fingerprint Dive into the research topics of 'Cross-species mechanical fingerprinting of cardiac myosin binding protein-C'. Together they form a unique fingerprint. (elsevier.com)
- Cross-species mechanical fingerprinting of cardiac myosin binding protein-C . Biophysical Journal , 104 (11), 2465-2475. (elsevier.com)
- Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. (clinicaltrials.gov)
- Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner. (mysciencework.com)
- Based on our recent finding that cardiac myosin binding protein C (cMyBP-C) phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. (mysciencework.com)
- We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases. (mysciencework.com)
- Myocardial injury post-ischemia has been thought to be the predominant initiating event triggering cardiac protein release and subsequent induction of AAbs. (onlinejacc.org)
- (5) explore whether cardiac myosin binding protein C (cMyBP-C), a sarcomeric regulatory protein that controls cardiac contractile and relaxation functions, can serve as an early indicator of cardiac dysfunction and patient outcome in acute coronary syndrome (ACS). (onlinejacc.org)
- These data demonstrate that myosin isoenzyme distribution in the adult heart is unaltered by ovariectomy, suggesting that estrogen loses its ability to regulate expression of this protein in the mature heart. (mysciencework.com)
- Most mutations have been identified in the β myosin heavy chain (βMHC) gene, 2-11 and, less frequently, in the genes for cardiac myosin binding protein C, 12 α tropomyosin, 13 14 cardiac troponin T, 13 15 and myosin light chain. (bmj.com)
- Myocarditis may be induced experimentally by several methods, including immunization with protein ( 2 ) or protein fragments ( 3 , 4 , 5 ) derived from cardiac myosin or infection with cardiotropic viruses ( 6 , 7 , 8 ). (jimmunol.org)
- We focused our attention on cardiac α-myosin heavy chain (CAMHC) because it is the predominant protein expressed in the adult murine heart ( 10 , 11 ) and because several studies have shown that the α-chain is more immunogenic than the highly homologous cardiac β-myosin heavy chain (CBMHC) ( 12 , 13 ). (jimmunol.org)
- The Z-lines of human skeletal muscle cells, in contrast to those of cardiac myocytes, gave positive reactions for both NMHC II-A and NMHC II-B. The presence of a motor protein in the Z-lines and intercalated discs raises the possibility that these structures may play a more dynamic role in the contraction/relaxation mechanism of cardiac and skeletal muscle than has been previously suspected. (elsevier.com)
- Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. (elsevier.com)
- Cardiac myosin binding protein C: its role in physiology and disease. (ox.ac.uk)
- Myosin binding protein-C (MyBP-C) is a thick filament-associated protein localized to the crossbridge-containing C zones of striated muscle sarcomeres. (ox.ac.uk)
- The cardiac isoform is composed of eight immunoglobulin I-like domains and three fibronectin 3-like domains and is known to be a physiological substrate of cAMP-dependent protein kinase. (ox.ac.uk)
- Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. (jpt.com)
- Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. (frontiersin.org)
- AIM: The aim of the study was to compare the functional and structural properties of the motor protein, myosin, and isolated myocyte contractility in heart muscle excised from hypertrophic cardiomyopathy patients by surgical myectomy with explanted failing heart and non-failing donor heart muscle. (ox.ac.uk)
- This protein makes up part of the sarcomere and forms macromolecular filaments composed of multiple myosin subunits. (wikipedia.org)
- In addition, anti-cardiac myosin antibodies in sera or purified IgG from myocarditis and cardiomyopathy targeted the beta-adrenergic receptor and induced antibody-mediated cAMP-dependent protein kinase A (PKA) cell signaling activity in heart cells. (elsevier.com)
- Myosin light chain 3, or MYL3 for short, consists of a 195 amino acid isoform that is 22 kDa, and is involved in the regulation of Myosin, which is a protein that conducts ATP hydrolysis. (novusbio.com)
- Karsai, Árpád and Kellermayer, Miklós and Harris, Samantha P. (2013) Cross-Species Mechanical Fingerprinting of Cardiac Myosin Binding Protein-C. BIOPHYSICAL JOURNAL, 104 (11). (mtak.hu)
- A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows. (news-medical.net)
- Decreased RLC phosphorylation by conventional or conditional cMLCK gene ablation did not affect troponin-I or myosin-binding protein-C phosphorylation in vivo. (elsevier.com)
- We report an African American family with hypertrophic cardiomyopathy in which an individual with severe disease has alterations in two sarcomeric protein genes, cardiac beta-myosin heavy chain (MYH7) and troponin I (TNNI3). (cdc.gov)
- We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. (haldanessieve.org)
- Despite the temperature sensitivity of the mutant large tumor antigen protein, a subset of transgenic mice in several lineages developed marked cardiac and skeletal myopathies. (elsevier.com)
- Myosin binding protein C (MyBPC) is essential for the structure of the sarcomeres in striated muscle. (diva-portal.org)
- The patient expressed the cardiac specific MyBPC isoform in skeletal muscle at transcript and protein levels. (diva-portal.org)
Isoform15
- The cMyBP-C isoform expressed in cardiac muscle differs from those expressed in slow and fast skeletal muscle (MYBPC1 and MYBPC2, respectively) by three features: (1) an additional immunoglobulin (Ig)-like domain on the N-terminus, (2) a linker region between the second and third Ig domains, and (3) an additional loop in the sixth Ig domain. (wikipedia.org)
- During normal physiology, beta-cardiac MHC is the predominant form, with the alpha-isoform contributing around only 7% of the total MHC. (abcam.com)
- The absence of cMyBP-C in the t/t and the unphosphorylated cMyBP-C in the AllP{sub -t/t} both resulted in a shorter myosin cross-bridge lifetime when myosin isoform was controlled. (osti.gov)
- The isoform composition of myosin light chains and the extent of their phosphorylation in skeletal and cardiac muscles of ground squirrel Citellus undulatus in different periods of hibernation were studied. (unboundmedicine.com)
- During hibernation, a shift of isoform composition of essential and regulatory skeletal muscle myosin light chains toward slower isoforms was observed, which is evidenced by the data obtained on m. psoas and on the totality of all skeletal muscles. (unboundmedicine.com)
- A possible role of posttranslation changes in myosin light chains and their isoform shifts in the hibernation scenario is discussed. (unboundmedicine.com)
- These novel results suggest that the heart-specific UNC-45b isoform functions as a molecular chaperone mediating contractile function of the sarcomere and gene expression in cardiac development. (biologists.org)
- Here we present the solution structure of one part of the N-terminal binding site, the third immunoglobulin domain of the cardiac isoform of human MyBP-C (cC2) together with a model of its interaction with myosin. (semanticscholar.org)
- MYBPC3, the cardiac isoform, is expressed exclussively in heart muscle. (mybiosource.com)
- The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. (kent.ac.uk)
- For these parameters, a-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow b isoform despite 91% sequence identity between the motor domains of a- and b-myosin. (kent.ac.uk)
- Since we previously demonstrated that chronic statin treatment modifies myosin heavy chain isoform pattern in skeletal muscle impairing its functional properties, this work was aimed at investigating the effects of statin chronic treatment on both ventricle ubiquinone content and myosin heavy chain isoforms. (scirp.org)
- There is one cardiac specific isoform and two skeletal muscle specific isoforms. (diva-portal.org)
- Mutations in MYBPC3 encoding the cardiac isoform cause cardiomyopathy. (diva-portal.org)
- Numerous muscle fibres expressing the mutant cardiac isoform showed structural abnormalities with disorganisation of sarcomeres and depletion of myosin thick filaments. (diva-portal.org)
Hypertrophic18
- Histologically, Mybpc3-targeted knock-out hearts display structural rearrangements with cardiac myocyte disarray and increased interstitial fibrosis similar to patients with hypertrophic cardiomyopathy, without obvious alterations in shape or size of single cardiac myocytes. (wikipedia.org)
- MYBPC3 was thus the fourth gene for hypertrophic cardiomyopathy, following MYH7, encoding β-myosin heavy chain, TNNT2 and TPM1, encoding cardiac troponin T and α-tropomyosin, respectively, earmarking hypertrophic cardiomyopathy as a disease of the sarcomere. (wikipedia.org)
- CK-274 is a novel cardiac myosin inhibitor, discovered by company scientists, in development for the potential treatment of hypertrophic cardiomyopathy (HCM). (yahoo.com)
- Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. (osti.gov)
- I (J.A.S.) was asked to preface my talk at the 2015 Journal of Experimental Biology Symposium on Muscle: Molecules to Motion with a brief historical perspective of my laboratory's specific contributions to research on actin and myosin, and how those contributions led to our current focus on understanding the molecular basis of hypertrophic and dilated cardiomyopathy. (biologists.org)
- Hypertrophic cardiomyopathy (HCM) is the most frequently occurring inherited cardiac disease, affecting more than 1 in 500 individuals ( 1 ), and 10% of HCM patients develop fatal arrhythmia and/or heart failure ( 2 ). (sciencemag.org)
- Both mutations were predicted to disrupt the high-affinity, C-terminal myosin-binding domain of cardiac MyBP-C. Again, findings demonstrated that as in the case of the 3 forms that had been defined in molecular terms previously, familial hypertrophic cardiomyopathy is a disease of the sarcomere. (cloud-clone.com)
- To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype. (nih.gov)
- Missense mutations in alpha-cardiac actin (ACTC) have been associated with both hypertrophic and dilated cardiomyopathies (HCM and DCM respectively). (uoguelph.ca)
- Objective To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with β myosin heavy chain (βMHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. (bmj.com)
- Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. (elsevier.com)
- Mutations in the gene encoding cardiac MyBP-C are a common cause of hypertrophic cardiomyopathy, and this has led to increased interest in the protein's function. (ox.ac.uk)
- In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca 2+ sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2 . (frontiersin.org)
- The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy. (ox.ac.uk)
- The presence of a myosin heavy chain mutation causing hypertrophic cardiomyopathy can be predicted from a simple functional assay. (ox.ac.uk)
- Current research is being conducted on the relationship between Myosin light chain 3 and a multitude of diseases and disorders, including familial hypertrophic cardiomyopathy, congestive heart failure, restrictive cardiomyopathy, dilated cardiomyopathy, diabetes mellitus, and renal failure. (novusbio.com)
- Familial hypertrophic cardiomyopathy associated with cardiac beta-myosin heavy chain and troponin I mutations. (cdc.gov)
- Variation in the human β-cardiac myosin gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. (haldanessieve.org)
Contractility13
- This publication reveals, for the first time in a peer reviewed journal, the mechanism of action for omecamtiv mecarbil and the scientific rationale for directly modulating cardiac contractility as an innovative therapeutic strategy for improving cardiac performance in patients with heart failure. (redorbit.com)
- The authors recognized that decreased cardiac contractility is a central feature of systolic heart failure and that there is a need for more safe and effective treatment options to improve cardiac contractility. (redorbit.com)
- Existing drugs that increase cardiac contractility do so indirectly through signaling cascades but their use is limited by their mechanism-related adverse effects. (redorbit.com)
- In preclinical models, CK-274 reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. (yahoo.com)
- CK-274 reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility. (yahoo.com)
- In preclinical models of cardiac function, CK-274 reduced cardiac contractility in a predictable dose and exposure dependent fashion. (yahoo.com)
- Measurements of heart stiffness and phosphorylation of the myosin regulatory light chains showed that BDM, Y-27632, and blebbistatin significantly reduced myocardial contractility, while ML-7 had a lesser effect. (springer.com)
- The isoenzymic changes could account for the decreases in both myosin ATPase activity and cardiac contractility described previously in our laboratory and by others. (ahajournals.org)
- Currently available inotropes, such as dobutamine and milrinone, increase cardiac contractility at the expense of increased intracellular concentrations of calcium and cAMP, contributing to increased heart rate, hypotension, arrhythmias, and mortality. (escholarship.org)
- Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure. (clinicaltrials.gov)
- Accompanying this dilatation is a concomitant loss of myocyte contractility that often leads to decreased cardiac output and large-scale multiorgan failure ( 1 ). (jimmunol.org)
- Teerlink JR, et al "Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): Results from a double-blind, randomized, placebo-controlled, multicenter study" AHA 2015. (medpagetoday.com)
- Thus, statins which are prescribed to prevent cardiovascular disease, might induce cardiac metabolic and structural modifications whose functional implications on contractility are still to be established and carefully considered. (scirp.org)
Sarcomere6
- cMyBP-C is not essential for sarcomere formation during embryogenesis, but is crucial for sarcomere organization and maintenance of normal cardiac function. (wikipedia.org)
- Furthermore, cMyBP-C contributes to the regulation of cardiac contraction at short sarcomere length and is required for complete relaxation in diastole. (wikipedia.org)
- When striated (skeletal and cardiac) muscle is in its relaxed state, myosin motors are packed in helical tracks on the surface of the thick filament, folded toward the center of the sarcomere, and unable to bind actin or hydrolyze ATP (OFF state). (ovid.com)
- We hypothesize that these mutations affect the biomechanical properties of myosin, such as increasing its intrinsic force and/or its duty ratio and therefore the ensemble force of the sarcomere. (sciencemag.org)
- Finally, we have proposed a new structural model of the cardiac muscle sarcomere that includes connectin filaments. (rupress.org)
- Cardiac myosin light chain kinase (cMLCK) phosphorylates ventricular myosin regulatory light chain 2 (MLC2v) and regulates sarcomere and cardiomyocyte organization. (cdc.gov)
Contraction20
- cMyBP-C appears to act as a brake on cardiac contraction, as loaded shortening, power and cycling kinetics all increase in cMyBP-C knockout mice. (wikipedia.org)
- In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of cardiac contraction. (redorbit.com)
- Cardiac muscle contraction is powered by ATP hydrolysis during cycles of interaction between myosin-containing thick filaments and actin-containing thin filaments. (pnas.org)
- To inhibit contraction, embryonic chick hearts at stages 10-12 (10-16 somites, 33-48 h) were exposed to the myosin inhibitors 2,3-butanedione monoxime (BDM), ML-7, Y-27632, and blebbistatin. (springer.com)
- Goeckeler ZM, Wysolmerski RB (1995) Myosin light chain kinase-regulated endothelial cell contraction: the relationship between isometric tension, actin polymerization, and myosin phosphorylation. (springer.com)
- The known interactions of UNC-45b as a molecular chaperone are consistent with diminished accumulation of the sarcomeric myosins, but not their mRNAs, and the resulting decreased contraction of homozygous mutant embryonic hearts. (biologists.org)
- Cardiac contraction is essential for viability. (biologists.org)
- In vitro studies have demonstrated that these agents increase the rate of effective myosin cross-bridge formation, increasing the duration and amount of myocyte contraction, and inhibit non-productive consumption of ATP, potentially improving myocyte energy utilization, with no effect on intracellular calcium or cAMP. (escholarship.org)
- Structure of the actin-myosin complex and its implications for muscle contraction. (nature.com)
- Dynamic measurement of myosin light-chain domain tilt and twist in muscle contraction. (nature.com)
- Myosin is defined as a mechano-enzyme molecule which converts the chemical energy stored as adenosine triphosphate (ATP) into mechanical energy (muscle contraction). (who.int)
- Myosins ( / ˈ m aɪ ə s ɪ n , - oʊ -/ [1] [2] ) are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes . (wikipedia.org)
- ORLANDO -- The novel agent omecamtiv mecarbil might improve cardiac contraction characteristics in heart failure with reduced ejection fraction (HFrEF), an early-phase study suggested. (medpagetoday.com)
- Omecamtiv is a selective cardiac myosin activator, which Teerlink described as "more hands pulling on the rope" for force production in contraction. (medpagetoday.com)
- For example, myosin-II motors power muscle contraction, whereas myosin-V motors engage in intracellular transport. (elifesciences.org)
- Myosin light chain 3 has been linked to the RhoA pathway, as well as PKA signaling, growth cone motility, cell adhesion, cardiac muscle contraction, and cytoskeleton remodeling. (novusbio.com)
- sensitivity of myofilament contraction necessary for normal cardiac performance. (elsevier.com)
- abstract = "In beating hearts, phosphorylation of myosin regulatory light chain (RLC) at a single site to 0.45 mol of phosphate/mol by cardiac myosin light chain kinase (cMLCK) increases Ca2+ sensitivity of myofilament contraction necessary for normal cardiac performance. (elsevier.com)
- Phosphorylation of myosin II plays an important role in many cell functions, including smooth muscle contraction. (biomedsearch.com)
- Myosin motors are the fundamental force-generating element of muscle contraction. (haldanessieve.org)
Gene12
- Cardiac development requires interplay between the regulation of gene expression and the assembly of functional sarcomeric proteins. (biologists.org)
- This gene encodes the alpha heavy chain subunit of cardiac myosin. (mybiosource.com)
- The gene is located ~4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. (mybiosource.com)
- A gene on chromosome 14q12 that encodes a heavy chain of myosin and is thus involved in cytokinesis, cell shape and specialised functions-e.g., secretion and capping. (thefreedictionary.com)
- The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. (frontiersin.org)
- and related to mutations in the MYL2 gene encoding for the ventricular and slow-twitch skeletal myosin regulatory light chain (RLC). (frontiersin.org)
- cardiac myosin heavy chain (MyHC) gene that cause HCM, but the underlying molecular effects on the myosin molecule remain elusive. (grantome.com)
- Mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain IIA, have been recently reported in three syndromes that share the association of macrothrombocytopenia (MTCP) and leukocyte inclusions: the May-Hegglin anomaly and Sebastian and Fechtner syndromes. (asnjournals.org)
- Indeed, mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain IIA, were subsequently identified in patients affected with these diseases ( 9 - 11 ). (asnjournals.org)
- Morkin, E. (2000) Control of cardiac myosin heavy chain gene expression. (scirp.org)
- Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy. (cdc.gov)
- To examine the relationships between cardiocyte proliferation and differentiation, we tested the ability of a fragment from the rat β myosin heavy-chain (MHCβ) gene to correctly target expression of a thermolabile simian virus 40 large tumor antigen allele (tsA58) in the developing mouse. (elsevier.com)
ATPase7
- Measurement of calcium activated myosin ATPase activity when bound to thin filaments. (cytoskeleton.com)
- The purified myosin S1 fragment has been determined to be biologically active in an F-actin activated ATPase assay (see biological activity assay). (cytoskeleton.com)
- In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. (mybiosource.com)
- Actin-activated ATPase rates measured showed the E99K ACTC variant increased the ATPase rate of skeletal myosin by approximately 30% compared to WT ACTC. (uoguelph.ca)
- The IVS6-1 myosin demonstrated a significantly lower V max of the actin-activated myosin ATPase activity compared with WT. (frontiersin.org)
- In this paper, we have evaluated the potential of several in silico approaches to predict the target, antitarget and physicochemical profile of ( S )-blebbistatin, the best-known myosin II ATPase inhibitor, and a series of analogs thereof. (frontiersin.org)
- The pyrroloquinolinone ( S )-blebbistatin, ( S )- 1 in Figure 1 , is a cell-permeable, micromolar ATPase cycle inhibitor of myosin II. (frontiersin.org)
Chains7
- Regulatory myosin light chains of skeletal muscles of hibernating ground squirrels were completely dephosphorylated, while 25% of these light chains in active animals were phosphorylated. (unboundmedicine.com)
- In the atrial myocardium of hibernating ground squirrels, ventricular myosin light chains 1 (up to 60%) were registered. (unboundmedicine.com)
- In contrast, during arousal of ground squirrels, in ventricular myocardium the appearance of atrial myosin light chains 1 (up to 30%) was revealed. (unboundmedicine.com)
- TY - JOUR T1 - [Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods of hibernation]. (unboundmedicine.com)
- The myosin and its light chains used to produce the myosin S1 fragment was determined to be 90% pure (see Figure2). (cytoskeleton.com)
- The neck domain can also serve as a binding site for myosin light chains which are distinct proteins that form part of a macromolecular complex and generally have regulatory functions. (wikipedia.org)
- Specifically, newly-identified acetyl-proteins include Ca 2+ -handling proteins, RyR2 and SERCA2, and the myofilament proteins, myosin heavy chain, myosin light chains and subunits of the Troponin complex, among others. (plos.org)
Abstract2
- Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and Contractile Activities of the Myosin Motor. (ahajournals.org)
- abstract = "The mechanisms regulating cardiac muscle differentiation and development are incompletely understood. (elsevier.com)
Proteins10
- The expression and function of the cardiogenic transcription factors and the contractile and calcium regulatory proteins that assemble into the sarcomeres of the differentiated cardiac myocytes have been central to molecular studies of cardiac development. (biologists.org)
- We are beginning to understand how disruption of such processes allows exposure of cardiac proteins that are no longer being recognized as "self" and thus activate the adaptive immune response to trigger inflammation. (onlinejacc.org)
- Antibodies targeted to several cardiac proteins, including troponin I and beta adrenergic receptors, among others, have been identified in patients with DCM, HCM, and ischemic HF (1) . (onlinejacc.org)
- To understand the role of nonmuscle myosin II in cardiac and skeletal muscle, we used a number of polyclonal antibodies, three detecting nonmuscle myosin heavy chain II-B (NMHC II-B) and two detecting NMHC II-A, to examine the localization of these two proteins in fresh-frozen, acetone-fixed sections of normal human and mouse hearts and human skeletal muscles. (elsevier.com)
- In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. (frontiersin.org)
- Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. (frontiersin.org)
- The nomenclature can therefore be somewhat confusing when attempting to compare the functions of myosin proteins within and between organisms. (wikipedia.org)
- Similar filament-forming myosin proteins were found in cardiac muscle, smooth muscle, and nonmuscle cells. (wikipedia.org)
- However, beginning in the 1970s, researchers began to discover new myosin genes in simple eukaryotes [3] encoding proteins that acted as monomers and were therefore entitled Class I myosins. (wikipedia.org)
- This paper focuses on the use of such techniques for the multitarget (target and antitargets) design of inhibitors of myosins, the ATP-driven molecular motor proteins of the eukaryotic cell ( Sweeney and Houdusse, 2010 ). (frontiersin.org)
Myocytes5
- NMHC II-B was diffusely distributed in the cytoplasm of cardiac myocytes during development, but after birth it was localized to the Z-lines and intercalated discs. (elsevier.com)
- Whereas endothelial cells, smooth muscle cells and fibroblasts showed strong immunoreactivity for NMHC II-A and NMHC II-B, cardiac myocytes only showed reactivity for the latter. (elsevier.com)
- The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. (elsevier.com)
- Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C -/- ) mice were attached between a force transducer and position motor. (elsevier.com)
- RLC is slowly dephosphorylated in both noncontracting hearts and isolated cardiac myocytes from adult mice. (elsevier.com)
Isoforms7
- Cardiac MHC exists as two isoforms in humans, alpha-cardiac MHC and beta-cardiac MHC. (abcam.com)
- These studies provide first evidence for the localization of HDAC3 on sarcomeres and uncover a novel mechanism regulating the motor activity of cardiac MHC isoforms. (ahajournals.org)
- The distribution of myosin light chain-1 isoforms was measured by two-dimensional electrophoresis. (ox.ac.uk)
- Technical challenges have been faced in studying the disease using animal models due to differences in background composition of myosin isoforms between species, and previous work using non- human myosin has produced mixed results. (grantome.com)
- Virtually all eukaryotic cells contain myosin isoforms . (wikipedia.org)
- While different mammalian species express different proportions of a and b myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (a:b) while failing human ventricles express no detectable a-myosin. (kent.ac.uk)
- The modulation of heart contractile properties could be explained by the decrease of ventricle ubiquinone content and/or by putative changes in proportion of the different myosin heavy chain isoforms. (scirp.org)
MYH73
- This study functionally characterized the motor domains of five Dilated cardiomyopathy - causing mutations in human beta-cardiac myosin, MYH7. (antikoerper-online.de)
- Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal cardiac magnetic resonance (CMR) findings. (antikoerper-online.de)
- Genetic variants in the β-myosin heavy chain encoded by MYH7 involving the so-called "converter region" have been associated with early disease and higher rates of transplant and malignant arrhythmias. (revespcardiol.org)
Troponin3
- This means that their assessment is reliant on the use of blood tests measuring biomarkers such as cardiac Troponin (cTn) to exclude a heart attack. (plexusmd.com)
- While there was a "small increase in troponin I," it was "without imbalance in cardiac adverse events," Teerlink said. (medpagetoday.com)
- We generally have viewed release of troponin as a sign of cardiac injury," he said in an interview. (medpagetoday.com)
Activator6
- Omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin, was developed to address these limitations. (redorbit.com)
- Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of multiple Phase I and Phase IIa trials conducted under Cytokinetics' sponsorship. (redorbit.com)
- Late Breaking Trials: "The Selective Cardiac Myosin Activator, CK-1827452, Increases Systolic Function in Heart Failure" (Oral Presentation 564a on Monday, June 16, 2008, during the Late Breaking Trials session, 11:00 a.m. - 12:30 p.m. (marketwired.com)
- Cytokinetics' lead compound from this program, CK-1827452, a novel small molecule cardiac myosin activator, entered Phase II clinical trials for the treatment of heart failure in 2007. (marketwired.com)
- In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure. (ahajournals.org)
- A first-in-human study in healthy volunteers with the lead cardiac myosin activator, CK-1827452, as well as preliminary results from a study in patients with stable chronic heart failure, have extended these findings to humans, demonstrating significant increases in systolic ejection time, fractional shortening, stroke volume, and cardiac output. (escholarship.org)
Mutation5
- Therefore, the effects of the dwarf mutation on myosin isozymes can be explained by the lack of thyroid hormone in these animals. (rupress.org)
- Notably, the mutation disrupted the RLC-MHC interaction and the steady-state and kinetics of the acto-myosin interaction. (frontiersin.org)
- One myectomy myosin sample produced a consistently higher sliding speed than donor heart myosin and was identified with a disease-causing heavy chain mutation (V606M). (ox.ac.uk)
- This study will be the first study to clarify the primary effect of mutation in human cardiac myosin for these mutations. (grantome.com)
- Based on these findings, we propose that the TNNI3 Pro82Ser alteration is likely a disease-modifying mutation in a severely affected individual, and, furthermore, carriers of this alteration (3% of African Americans) might be at increased risk of late-onset cardiac hypertrophy. (cdc.gov)
Hypertrophy8
- Absence of cMyBP-C (Mybpc3-targeted knock-out mice) results in severe cardiac hypertrophy, increased heart-weight-to-body-weight-ratios, enlargement of ventricles, increased myofilament Ca2+ sensitivity and depressed diastolic and systolic function. (wikipedia.org)
- In preclinical models of disease, CK-274 reduced compensatory cardiac hypertrophy and cardiac fibrosis. (yahoo.com)
- These data suggest that hemodynamic load and/or neural innervation are necessary for hypertrophy associated with chronic conditioning by swimming, whereas myosin isoenzyme control is significantly mediated by humoral factors. (ahajournals.org)
- Myosin isoenzyme changes in several models of rat cardiac hypertrophy. (ahajournals.org)
- In all models of cardiac hypertrophy, an isoenzymic redistribution was observed with a significant increase in V3. (ahajournals.org)
- To test whether MHC acetylation was sensitive to cardiac stress, we examined MHC acetylation during development of isoproterenol-induced hypertrophy of the heart. (ahajournals.org)
- In the inducible transgenic group, MMI ‐0100 treatment reduced cardiac fibrosis, decreased cardiac hypertrophy, and prolonged survival. (ahajournals.org)
- Provides proof of principle that MMI‐0100 treatment reduced cardiac fibrosis, decreased cardiac hypertrophy, and prolonged survival under conditions where the primary disease‐causing peptide was continually made. (ahajournals.org)
Cardiomyopathy2
- Our in vitro results suggest that when placed in vivo , IVS6-1 may lead to cardiomyopathy and early death of homozygous infants by severely compromising the ability of myosin to develop contractile force and maintain normal systolic and diastolic cardiac function. (frontiersin.org)
- In addition, we have defined disease specific peptide epitopes in the human cardiac myosin rod S2 region in human myocarditis and cardiomyopathy as well as a mechanistic role of autoantibody in the pathogenesis of disease. (elsevier.com)
Beta-cardiac2
- human alpha- and beta-cardiac myosin, as well as the mutants, show opposite mechanical and enzymatic phenotypes with respect to each other. (antibodies-online.com)
- Direct binding studies show that the UNC-45b chaperone forms physical complexes with both the alpha and beta cardiac myosins and the cardiogenic transcription factor GATA4. (biologists.org)
Filaments9
- Elastic filaments in situ in cardiac muscle: deep-etch replica analysis in combination with selective removal of actin and myosin filaments. (rupress.org)
- To clarify the full picture of the connectin (titin) filament network in situ, we selectively removed actin and myosin filaments from cardiac muscle fibers by gelsolin and potassium acetate treatment, respectively, and observed the residual elastic filament network by deep-etch replica electron microscopy. (rupress.org)
- Close comparison of these images with the replica images of intact and S1-decorated sarcomeres led us to conclude that, in intact sarcomeres, the elastic filaments were laterally associated with myosin and actin filaments in the A and I bands, respectively. (rupress.org)
- The generation of force and shortening in striated muscle (skeletal and cardiac) is due to the cyclic ATP-driven interactions of myosin motors emerging from the thick filament with the neighboring thin, actin-containing filaments. (rupress.org)
- Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. (nature.com)
- RESULTS: The fraction of actin filaments moving when powered by myectomy myosin was 21% less than with donor myosin (P = 0.006), whereas the sliding speed was not different (0.310 +/- 0.034 for myectomy myosin vs. 0.305 +/- 0.019 microm/s for donor myosin in six paired experiments). (ox.ac.uk)
- Presumably this is so the myosins may interact, via their tails, with a large number of different cargoes, while the goal in each case - to move along actin filaments - remains the same and therefore requires the same machinery in the motor. (wikipedia.org)
- For example, in muscle, myosin-II motors are arranged into multimeric arrays called thick filaments and the individual motors typically have a strong preference for the actin free state (i.e. low duty ratio). (elifesciences.org)
- In contrast, individual myosin-Va motors have high duty ratios (i.e. prefer the actin-bound state), helping them to processively walk along actin filaments in intracellular transport. (elifesciences.org)
Recombinant Human3
- Using recombinant human β-cardiac myosin, we characterize the molecular effects of three severe HCM-causing converter domain mutations: R719W, R723G, and G741R. (sciencemag.org)
- We report here fast-kinetic analysis of recombinant human a and b myosin heavy chain motor domains. (kent.ac.uk)
- Recombinant Human Myosin light cha. (novusbio.com)
Genes5
- We developed an human cardiac alpha-myosin -induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes. (antibodies-online.com)
- Human cardiac myosin heavy chain genes. (nature.com)
- [3] Following the discovery by Pollard and Korn (1973) of enzymes with myosin-like function in Acanthamoeba castellanii , a global range of divergent myosin genes have been discovered throughout the realm of eukaryotes. (wikipedia.org)
- The wide variety of myosin genes found throughout the eukaryotic phyla were named according to different schemes as they were discovered. (wikipedia.org)
- The transcriptional regulation of C. elegans myosin genes is in many respects similar to that of vertebrates. (biologists.org)
Interaction4
- cMyBP-C regulates the positioning of myosin and actin for interaction and acts as a tether to the myosin S1 heads, limiting their mobility. (wikipedia.org)
- This raises the question of whatthe mechanism is that integrates the Ca 2+ -dependent thin filament activation, making myosin heads available for interaction with actin. (ovid.com)
- Several structural models of the interaction of MyBP-C with myosin have been proposed, although its precise arrangement on the thick filament remains to be elucidated. (ox.ac.uk)
- The tail domain generally mediates interaction with cargo molecules and/or other myosin subunits . (wikipedia.org)
Molecular8
- The results are discussed in terms of the molecular structure and the functional properties of various myosins. (rupress.org)
- Brand T (2003) Heart development: molecular insights into cardiac specification and early morphogenesis. (springer.com)
- My laboratory, over the last several decades, has been devoted to developing both in vivo and in vitro systems to understand the molecular basis of energy transduction by the myosin family of molecular motors ( Spudich, 2011 , 2012 ). (biologists.org)
- Three-dimensional structure of myosin subfragment-1: a molecular motor. (nature.com)
- These results demonstrate deficiencies in myosin binding of the E99K ACTC variant, providing insight into the primary molecular disruptions leading to the development of cardiomyopathies. (uoguelph.ca)
- To test this hypothesis, we modeled the distribution of conformations for 12 myosin motor domains by building Markov state models (MSMs) from an unprecedented two milliseconds of all-atom, explicit-solvent molecular dynamics simulations. (elifesciences.org)
- A ligand-based method using molecular fingerprints was, however, able to select actives for myosin II inhibition. (frontiersin.org)
- In conclusion, in the search for ( S )-blebbistatin analogs, the dissimilarity distance of molecular fingerprints to known actives and the computed antitarget and physicochemical profile of the molecules can be used for compound design for molecules with potential as tools for modulating myosin II and motility-related diseases. (frontiersin.org)
Molecule8
- CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its collaborations. (yahoo.com)
- Recently, the production of functional human myosin in vitro has been established by using a mammalian cell line system, and we now have the capacity to obtain pure human cardiac myosin for functional analysis at the single molecule level. (grantome.com)
- cardiac myosin molecules will be measured using laser trap single molecule analysis. (grantome.com)
- cardiac myosin at the single-molecule level. (grantome.com)
- [5] The power stroke occurs at the release of phosphate from the myosin molecule after the ATP hydrolysis while myosin is tightly bound to actin. (wikipedia.org)
- The release of the ADP molecule leads to the so-called rigor state of myosin. (wikipedia.org)
- [6] The binding of a new ATP molecule will release myosin from actin. (wikipedia.org)
- The data demonstrated that two monoclonal antibodies against streptococci were specific for skeletal muscle and/or cardiac myosin and for subfragments of the myosin molecule. (jimmunol.org)
Novel cardiac1
- This approach is made possible with the novel cardiac myosin-activating compound omecamtiv mecarbil (formerly called CK-1827452). (ahajournals.org)
Function of myosin1
- The structure and function of myosin is globally conserved across species, to the extent that rabbit muscle myosin II will bind to actin from an amoeba . (wikipedia.org)
Phosphorylation of cardiac myosin1
- Cardiac-specific myosin light chain kinase (cMLCK) is the kinase predominantly responsible for the maintenance of the basal level of phosphorylation of cardiac myosin light chain 2 (MLC2), which it phosphorylates at Ser-15. (go.jp)
Myocardial4
- Animal models have shown that this novel mechanism increases the systolic ejection time, resulting in improved stroke volume, fractional shortening, and hemodynamics with no effect on myocardial oxygen demand, culminating in significant increases in cardiac efficiency. (escholarship.org)
- This appears to occur when the supply of cardiac self-antigens increases after a myocardial insult, resulting in persistent induction of antigen-specific T cells that induce B cell production of AAbs to such antigens (2) and likely contribute the intensity of inflammation in myocardial structures found in patients with HF. (onlinejacc.org)
- Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. (jpt.com)
- The enzyme is inhibited by statins that, besides lowering cholesterolemia, seem to impair human energy-dependent myocardial functions (e.g. stroke volume, cardiac output, and contractile index). (scirp.org)
Kinetics5
- Phosphorylation of cMyBP-C increases the force and kinetics of twitches in living cardiac muscle. (nih.gov)
- Ebus JP, Stienen GJ (1996) Effects of 2,3-butanedione monoxime on cross-bridge kinetics in rat cardiac muscle. (springer.com)
- A new class of pharmacologic agents, cardiac myosin activators, directly targets the kinetics of the myosin head. (escholarship.org)
- In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the k obs -[MgATP] relationship compared to WT. (frontiersin.org)
- These differences stem from variations in the tunings of the thermodynamics and kinetics of the individual steps of the myosins' conserved mechanochemical cycle, which couples ATP hydrolysis to actin binding and the swing of a lever arm ( De La Cruz and Ostap, 2004 ). (elifesciences.org)
Antibodies6
- Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. (jpt.com)
- A study of anti-group A streptococcal monoclonal antibodies cross-reactive with myosin. (jimmunol.org)
- Two of the anti-streptococcal monoclonal antibodies were previously shown to cross-react with muscle myosin. (jimmunol.org)
- By Western immunoblotting and competitive inhibition assays, monoclonal antibodies 36.2.2 and 54.2.8 both were found to react with the heavy chain of skeletal muscle myosin. (jimmunol.org)
- The specificity of the monoclonal antibodies for subfragments of skeletal muscle myosin indicated that monoclonal antibody 36.2.2 was specific for light meromyosin fragments, whereas 54.2.8 reacted with both heavy and light meromyosin. (jimmunol.org)
- The reactions of the monoclonal antibodies with human tissue sections were consistent with the immunochemical reactions of the monoclonal antibodies with both denatured and native myosin. (jimmunol.org)
Skeletal and cardiac1
- Hereditary pituitary dwarfism in mice affects skeletal and cardiac myosin isozyme transitions differently. (rupress.org)
Myopathy2
- Fishman, Glenn I. / Cardiac and skeletal myopathy in β myosin heavy-chain simian virus 40 tsA58 transgenic mice . (elsevier.com)
- The surprising identification of a skeletal myopathy in this patient was due to aberrant expression of mutant cardiac MyBPC in skeletal muscle. (diva-portal.org)
Human13
- Phosphorylation is required for normal cardiac function and cMyBP-C stability, and overall phosphorylation levels of cMyBP-C are reduced in human and experimental heart failure. (wikipedia.org)
- Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. (osti.gov)
- Despite numerous studies, most performed with non-human or non-cardiac myosin, there is no clear consensus about the mechanism of action of these mutations on the function of human β-cardiac myosin. (biologists.org)
- We are using a recombinantly expressed human β-cardiac myosin motor domain along with conventional and new methodologies to characterize the forces and velocities of the mutant myosins compared with wild type. (biologists.org)
- These results indicate that the net biomechanical properties of human β-cardiac myosin carrying these converter domain mutations are very similar to those of wild type or are even slightly hypocontractile, leading us to consider an alternative mechanism for the clinically observed hypercontractility. (sciencemag.org)
- Stiff matrix induces switch to pure β-cardiac myosin heavy chain expression in human ESC-derived cardiomyocytes. (stembook.org)
- As suggested in a prospective human study, circulating AAbs to cardiac antigens can precede disease manifestation and may independently predict DCM development (3) . (onlinejacc.org)
- This represents the ?rst such analysis of any human muscle myosin motor and the ?rst of a-myosin from any species. (kent.ac.uk)
- In our study, we define the human cardiac myosin epitopes in human myocarditis and cardiomyopathies and establish a mechanism to explain how anti-cardiac myosin autoantibodies may contribute to heart disease. (elsevier.com)
- Antibody-mediated cell signaling of PKA was blocked by antigen-specific inhibition by human cardiac myosin or the beta-adrenergic receptor but not the alpha adrenergic receptor or bovine serum albumin. (elsevier.com)
- The data suggest that IgG antibody against human cardiac myosin reacts with the beta-adrenergic receptor and triggers PKA signaling in heart cells. (elsevier.com)
- In summary, we have identified a new class of crossreactive autoantibodies against human cardiac myosin and the beta-adrenergic receptor in the heart. (elsevier.com)
- Multi-dimensional structure function relationships in human β-cardiac myosin from population scale genetic variation. (haldanessieve.org)
Adult4
- These studies not only serve to understand embryonic development, but also have ramifications for cardiac remodeling in adult disease ( Wessels and Sedmera, 2003 ). (biologists.org)
- in contrast, the neonatal to adult fast myosin transition in hind limb skeletal muscle was slowed but not totally inhibited. (rupress.org)
- Ovariectomy fails to modify the cardiac myosin isoenzyme profile of adult rats. (mysciencework.com)
- Because hearts of this age are still undergoing significant maturation, the current study sought to determine if estrogen similarly regulates myosin isoenzyme expression in the mature adult heart. (mysciencework.com)
Light16
- Tryptic and chymotryptic light meromyosin paracrystals from red and cardiac muscles of rabbit show a negative and positive staining pattern with uranyl acetate and phosphotungstate that sharply differs from that of white muscle light meromyosin paracrystals. (rupress.org)
- Goeckeler ZM, Masaracchia RA, Zeng Q, Chew TL, Gallagher P, Wysolmerski RB (2000) Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2. (springer.com)
- Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. (antibodies-online.com)
- Myosin can be proteolytically cleaved into heavy meromyosin (HMM) and light meromyosin (LMM) by α-chymotrypsin in the presence of magnesium. (cytoskeleton.com)
- cMyBP-C binds to the LMM (light meromyosin) portion of the myosin rod via its C-terminal domain, C10. (ox.ac.uk)
- Dominguez, R., Freyzon, Y., Trybus, K. M. & Cohen, C. Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualisation of the pre-power stroke state. (nature.com)
- Immunoassay reagents intended to perform qualitative and/or quantitative analyses on a serum or plasma sample to determine myosin light chain (MLC). (optometricmanagement.com)
- MyBP-C contributes to thick filament structure via interactions at its C-terminus with the light meromyosin section of the myosin rod and with titin. (ox.ac.uk)
- The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). (elifesciences.org)
- We focus on the regulation of myosin light-chain phosphatase (MLCP), an enzyme comprised of a PP1 catalytic subunit and regulatory subunit MYPT1. (elifesciences.org)
- Myosin light chain-2 phosphorylation was measured by sodium dodecyl sulphate-polyacrylamide gel electrophoresis using Pro-Q Diamond phosphoprotein stain. (ox.ac.uk)
- This diversity is in part due to differences in myosins' tails and light chain-binding domains, which influence properties like localization and multimerization ( Krendel and Mooseker, 2005 ). (elifesciences.org)
- Myosin light chain 3 Overexpressio. (novusbio.com)
- Myosin light chain 3 Recombinant P. (novusbio.com)
- Electrically paced ventricular trabeculae restored RLC phosphorylation, which was increased to 0.91 mol of phosphate/mol of RLC with inhibition of myosin light chain phosphatase (MLCP). (elsevier.com)
- The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase (MP). (biomedsearch.com)
Fast skeletal muscle1
- studies compare cardiac alpha-myosin, beta-myosin, and fast skeletal muscle myosin. (antibodies-online.com)
Electrophoresis1
- Samples of the left and right ventricles were isolated from these hearts, and myosins were analyzed by electrophoresis in non-dissociating conditions. (ahajournals.org)
Regulation1
- Myosin phosphatase: structure, regulation and function. (biomedsearch.com)
Thick2
- The approximate stoichiometry of cMyBP-C along the thick filament is 1 per 9-10 myosin molecules, or 37 cMyBP-C molecules per thick filament. (wikipedia.org)
- This phosphorylation repels the myosin heads from the thick myosin filament and moves them toward the thin actin filament. (go.jp)
Tightly bound to actin1
- Overall, the cycle times are ten-fold faster for a-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. (kent.ac.uk)
Omecamtiv Mecarbil5
- Cytokinetics, Incorporated (Nasdaq: CYTK) announced today the publication of preclinical research in the March 18, 2011 issue of the journal Science regarding the activation of cardiac myosin by an investigational drug candidate, omecamtiv mecarbil, and the potential therapeutic role that this novel mechanism may play for patients with systolic heart failure. (redorbit.com)
- In this publication, the authors demonstrated that omecamtiv mecarbil binds to the myosin catalytic domain and acts by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. (redorbit.com)
- Paradoxically, omecamtiv mecarbil inhibits adenosine 5'-triphosphate (ATP) turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. (redorbit.com)
- Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. (ahajournals.org)
- The major differences between the effect of omecamtiv mecarbil on cardiac function and the effect induced by a catecholamine, for example, dobutamine, is that omecamtiv mecarbil did not increase LV dP/dt but rather increased LV systolic ejection time by 26±2.9% in sHF. (ahajournals.org)
Heart failure5
- The publication titled, "Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure," discusses the potential clinical role for therapies that directly activate cardiac myosin in the treatment of systolic heart failure. (redorbit.com)
- The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart failure. (redorbit.com)
- Decreased systolic function is a central factor in the pathogenesis of heart failure, yet there are no safe medical therapies to improve cardiac function in patients. (escholarship.org)
- These studies suggest that cardiac myosin activators offer the promise of a safe and effective treatment for heart failure. (escholarship.org)
- The contribution of T cells has been recognized as critical to cardiovascular conditions such as cardiac remodeling and heart failure (HF), and B cell-mediated production of autoantibodies (AAbs) has emerged as another potential mechanism contributing to HF development and progression (1) . (onlinejacc.org)
Mutations in patients1
- Data show that compound heterozygosity for recessive myosin heavy chain 6 (MYH6) mutations in patients with hypoplastic left heart and reduced systemic right ventricular ejection fraction. (antibodies-online.com)
Smooth muscle myosin2
- A smooth-muscle myosin heavy-chain assay is performed in the first 24 hours. (medscape.com)
- The smooth muscle myosin heavy-chain assay has greater sensitivity and specificity than transthoracic echocardiography (TTE), CT, and aortography, but it has less sensitivity and specificity than transesophageal echocardiography (TEE), MRI, and helical CT. (medscape.com)