Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of a cardiotonic agent, MCI-154 (6-[4-(4-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate), on the contractile properties and adenosine triphosphatase (ATPase) activity of chemically skinned rabbit skeletal muscle fibers. As in cardiac muscle, MCI-154 potentiated isometric tension and improved isometric tension cost at full Ca2+ activation. It showed little Ca2+-sensitizing effect. In contrast to its effect on cardiac muscle, however, MCI-154 decreased all the kinetic parameters tested (shortening velocity, the rate of rise of tension, and actomyosin ATPase activity). All the results are explainable if MCI-154 acts directly on skeletal actomyosin and inhibits a reaction step(s) of the ATPase cycle later than the force-generating event. The qualitative difference between cardiac and skeletal muscles in the responsiveness to this class of cardiotonic agents (MCI-154 and EMD 53998, a thiadiazinone derivative) is most readily understood if the agents have two independent actions, one on troponin and the other on actomyosin itself, the latter being dominant in skeletal muscle.
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PMID:Effect of a cardiotonic agent, MCI-154, on the contractile properties of skinned skeletal muscle fibers. 954 45

The heart has been recognized as a major target of thyroid hormone action. Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta1 (T3Rbeta1-delta337T) derived from the S kindred. The mutant receptor was originally identified in a patient with generalized resistance to thyroid hormone. Cardiac expression of the mutant receptor was achieved by a transgenic approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta) and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are known to be regulated by T3, their cardiac expression was analyzed. The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac muscle contraction was significantly prolonged in papillary muscles from transgenic mice. The electrocardiogram of transgenic mice showed a substantial prolongation of the QRS interval. Changes in cardiac gene expression, cardiac muscle contractility, and electrocardiogram are compatible with a hypothyroid cardiac phenotype despite normal T3 levels, indicating a dominant negative effect of the T3Rbeta mutant.
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PMID:Altered cardiac phenotype in transgenic mice carrying the delta337 threonine thyroid hormone receptor beta mutant derived from the S family. 992 21

The cardiac isoform of sarco(endo)plasmic reticulum Ca(2)(+) adenosine triphosphatase (SERCA2a) plays an important role in the contraction and relaxation of cardiac muscle. Phospholamban (PLN) and its homologue sarcolipin (SLN) are the endogenous regulators of SERCA2a. Evidence is accumulating that SERCA2a is intimately involved in the pathogenesis of cardiac hypertrophy and failure. Recent studies using genetically engineered animals revealed the implication of PLN for the development of cardiomyopathic phenotypes. This review focuses on advances in the understanding of molecular regulation of SERCA2a by PLN and SLN, and their implications for cardiac hypertrophy and failure in vivo.
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PMID:Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure. 1273 49

Intracellular calcium is a major coordinator of numerous aspects of cellular physiology, including muscle contractility and cell survival. In cardiac muscle, aberrant Ca(2+) cycling has been implicated in a range of pathological conditions including cardiomyopathies and heart failure. The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2. Recent evidence indicates that proteins of the Bcl-2 family can influence ER Ca(2+) content, a critical determinant of cellular sensitivity to apoptosis. The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.
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PMID:The role of SERCA2a/PLN complex, Ca(2+) homeostasis, and anti-apoptotic proteins in determining cell fate. 1841 21

1. Liver, kidney, brain, skeletal muscle, and cardiac muscle from one newborn and three adult long-snouted dolphins (Stenella plagiodon) were obtained for enzyme studies. 2. All of the dolphin tissues exhibited cytochrome oxidase, succinic dehydrogenase, and malic dehydrogenase activity. Considerable differences in the enzyme activities of the various tissues were noted, with cardiac muscle exhibiting the highest respiratory enzyme activity. The enzyme activities of dolphin tissues were lower than those of the corresponding rat tissues. 3. All of the dolphin tissues exhibited adenosine triphosphatase activity which was accelerated by magnesium and manganese but, in contrast to rat tissues, was only slightly activated by calcium. 4. Measurements of the distribution of acid-soluble phosphorus in dolphin tissues indicated that glycolysis in all of the tissues examined proceeded through the Emden-Meyerhof phosphorylation scheme. 5. The average glycogen content of dolphin skeletal muscle was 0.98 per cent as compared with 0.16 to 0.20 per cent for rat skeletal muscle. The high glycogen content of dolphin skeletal muscle indicates a ready source of substrate for glycolysis even during submergence when the blood supply may be differentially shunted to other organs. 6. Measurements of the organ weights of dolphins showed that the lungs occupy over three times and the liver one-half as much of the total body weight as do these organs in the rat. The heart and the thyroid gland of the dolphin are also larger in proportion to the total body weight than in the rat while the relative weights of the other tissues in the two species are about the same.
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PMID:Studies on the intermediary carbohydrate metabolism of aquatic animals; the distribution of acid-soluble phosphorus and certain enzymes in dolphin tissues. 1890 58

Muscle contraction results from force-generating interactions between myosin cross-bridges on the thick filament and actin on the thin filament. The force-generating interactions are regulated by Ca(2+) via specialised proteins of the thin filament. It is controversial how the contractile and regulatory systems dynamically interact to determine the time course of muscle contraction and relaxation. Whereas kinetics of Ca(2+)-induced thin-filament regulation is often investigated with isolated proteins, force kinetics is usually studied in muscle fibres. The gap between studies on isolated proteins and structured fibres is now bridged by recent techniques that analyse the chemical and mechanical kinetics of small components of a muscle fibre, subcellular myofibrils isolated from skeletal and cardiac muscle. Formed of serially arranged repeating units called sarcomeres, myofibrils have a complete fully structured ensemble of contractile and Ca(2+) regulatory proteins. The small diameter of myofibrils (few micrometres) facilitates analysis of the kinetics of sarcomere contraction and relaxation induced by rapid changes of [ATP] or [Ca(2+)]. Among the processes studied on myofibrils are: (1) the Ca(2+)-regulated switch on/off of the troponin complex, (2) the chemical steps in the cross-bridge adenosine triphosphatase cycle, (3) the mechanics of force generation and (4) the length dynamics of individual sarcomeres. These studies give new insights into the kinetics of thin-filament regulation and of cross-bridge turnover, how cross-bridges transform chemical energy into mechanical work, and suggest that the cross-bridge ensembles of each half-sarcomere cooperate with each other across the half-sarcomere borders. Additionally, we now have a better understanding of muscle relaxation and its impairment in certain muscle diseases.
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PMID:Insights into the kinetics of Ca2+-regulated contraction and relaxation from myofibril studies. 1916 98

Wilson's disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches.
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PMID:Wilson's disease: a comprehensive review of the molecular mechanisms. 2580 4


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