Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.4.1 (myosin ATPase)
1,140 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.
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PMID:Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats. 213 54

Cardiac myofibrils from cardiomyopathic hamsters exhibit elevated Mg2+ ATPase activity and a parallel upward shift of the calcium ATPase dose response curve. To explore the mechanism, myofibrils from control and cardiomyopathic hamster hearts were incubated with isolated troponin-tropomyosin complex (Tn.Tm) from cardiomyopathic and control hamster or from dog hearts. Tn.Tm from control hamster or dog hearts restored normal Mg2+ ATPase activities to myofibrils from myopathic hearts. However, the maximum ATPase response to calcium stimulation was less in cardiomyopathic myofibrils compared to controls, even when control Tn.Tm was included. Electrophoretic patterns of Tn.Tm from myopathic and control hearts were similar. Electrophoresis of the hamster myofibrils mixed with dog cardiac Tn.Tm and then washed demonstrated binding of this complex to myopathic myofibrils. To further confirm that the incubation experiments resulted in binding, 125I troponin-tropomyosin was cross-hybridized with myofibrils, extensively washed, and then analyzed enzymatically and autoradiographically. Autoradiograms demonstrated similar percent binding of 125I Tn.Tm to all myofibrillar preparations and enzymatic effects like those found using cold Tn.Tm. These studies suggest that Tn.Tm from cardiomyopathic hearts inhibits Mg2+ myofibrillar ATPase activity to a lesser degree than Tn.Tm from control hearts. Decreased stimulation by calcium in myopathic preparations may be due to abnormalities in troponin-tropomyosin and/or to the decreased myosin ATPase activity observed previously.
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PMID:Troponin-tropomyosin abnormalities in hamster cardiomyopathy. 214 67

We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)--secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101% vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P less than 0.05 vs. controls), whereas the maximum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32 +/- 5% vs. 8 +/- 2% in controls, P less than 0.001). Increased curvature of the force-velocity relationship (+64%, P less than 0.05 vs. controls) indicated that the muscles contracted more economically, suggesting the involvement of V3 myosin. Total calcium- and actin-activated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzymatic sites were involved in total ATPase activity. These data demonstrate that chronic GH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an increase in the number of active enzymatic sites.
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PMID:Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle. 214 10

Scallop adductor myosin is regulated by its subunits; the regulatory light chain (R-LC) and essential light chain (E-LC). Myosin light chains suppress muscle activity in the absence of calcium and are responsible for relaxation. The binding of Ca2+ to the myosin triggers contraction by releasing the inhibition imposed on myosin by the light chains. To map the functional domains of the R-LC, we have carried out mutagenesis followed by bacterial expression. Both wild-type and mutant proteins were hybridized to scallop myosin heavy chain/E-LC to map the regions of the light chain that are responsible for the binding to the myosin heavy chain/E-LC, for restoring the specific calcium-binding site, and controlling the myosin ATPase activity. The R-LC is expressed in Escherichia coli using the pKK223-3 (Pharmacia) expression vector and has been purified to greater than 90% purity. E. coli-expressed wild-type R-LC differs from the native R-LC by having the initiating methionine residue and an unblocked NH2 terminus. The wild-type R-LC restores Ca2+ binding and Ca2+ sensitivity when hybridized to scallop myosin. A point mutation of the sixth Ca2(+)-liganding position of domain I (Asp39----Ala39) results in a R-LC that binds more weakly to the heavy chain/E-LC and restores the specific Ca2(+)-binding site but not regulation of the actin-activated Mg2+ ATPase. A second mutation was produced by substituting the last 11 residues of the COOH terminus with 15 different residues. This mutant restores the specific Ca2(+)-binding site, but does not restore Ca2+ regulation to the actin-activated ATPase activity. Several other point mutations do not alter light chain function. The experiments directly establish that the divalent cation-binding site of domain I is functionally distinct from the specific Ca2(+)-binding site. The results indicate that an intact domain I and the COOH terminus are required to suppress the myosin ATPase activity. The fact that the domain I mutation and the COOH-terminal mutation disrupt regulation but do not affect Ca2(+)-binding indicates that these two aspects of regulation are separable and, therefore, the R-LC has distinct functional regions.
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PMID:Regulation of scallop myosin by mutant regulatory light chains. 214 99

After reviewing the controversies in the literature surrounding the regulation of oxidative phosphorylation, a unifying theory to integrate the disparate results would be welcome. Following the traditional biochemical approach to identifying sites of control, one searches for the rate-limiting step in a series of reactions (i.e. a biochemical pathway) that, presumably, will not be at equilibrium. This approach has not succeeded in locating a reaction in cardiac respiratory control that is singularly rate-limiting and may actually be contributing to, rather than clarifying, the problem. There are two major criticisms of this approach. First, even if the step is in disequilibrium, it does not prove that it is rate-limiting (26). Second, a reaction near equilibrium can contribute to regulation of a system (37). In a complex, multiple-reaction integrated pathway such as mitochondrial respiration there are many steps that could potentially share the control of the overall system. Thus this pathway easily lends itself to the possibility of multiple sites of control, each of which could contribute by varying degrees to regulation. In Figure 3 we present one possible network (undoubtedly incomplete) for the distributed control of respiration, which incorporates contributions by the cellular redox state (supply), phosphate metabolite concentrations (either kinetic or thermodynamic), and oxygen. The coordination of the dehydrogenases, phosphate metabolites, and myosin ATPase activity (work) may be orchestrated by a second messenger. Calcium is an attractive candidate for this role (15) as it simultaneously can modulate reducing equivalent supply via the dehydrogenases and ATP use by the myofibrils. The theory of shared control along the path of respiration is not new (37), and has been gaining support from a variety of laboratories (3, 9, 26). Applying this concept to the experimental setting, the relative control strengths for various steps in oxidative phosphorylation have been reported for isolated mitochondria (26). The control coefficients for respiration in isolated myocytes or hearts in vivo remain unknown at this time. If control of respiration occurs at multiple sites, it could account for much of the disagreement in the literature. Experimental conditions, whether intentional or inadvertent, that saturate one or more control mechanisms will increase the relative effect of the other regulatory sites on the remaining range of mitochondrial function. If, for example, the medium surrounding isolated myocytes is such that the cytosolic redox state and pO2 are very high, the phosphate metabolite concentrations could logically be expected to be a major factor influencing the observed rate of oxidative phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of mitochondrial respiration in the heart in vivo. 215 67

Thyroid hormone-induced changes in cardiac function have been recognized for over 150 years; however, the biochemical basis of triiodothyronine (T3) action in the heart has been intensely investigated only during the last two decades. T3-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. The c-erb A protein is the cellular homologue of the viral erythroblastosis A (v-erb A) protein, which causes red cell leukemia in chickens. Currently, three T3-binding isoforms of the c-erb protein and two non-T3-binding nuclear proteins that exert positive and negative effects on T3-responsive cardiac genes have been identified. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, thyroid hormone leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart.
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PMID:Biochemical basis of thyroid hormone action in the heart. 218 6

Histochemical analysis was used to study the relationship between Rana temporaria tibialis anterior and lumbricalis IV fibre cross-sectional areas and concentrations of myosin ATPase and NADH reductase. Both tonic and twitch fibre types were histochemically identified in each muscle and the twitch fibres were subgrouped into types 1, 2, and 3. Fibres that had the largest cross-sectional areas were identified as the fibres which contained the highest myosin ATPase activity and the lowest NADH reductase activity (type 1 fibres). However, this relationship was more pronounced in the tibialis anterior muscle. In addition, single fibres from both muscles were isolated and injected with Ca2+ indicator aequorin. The fibres isolated from the tibialis anterior muscle were those with the largest cross-sectional areas relative to other fibres within a given muscle. The force responses and Ca2+ transients recorded from this group of single fibres were found to be fairly uniform, which may suggest that a single type of fibre was isolated. In contrast, the physiological properties of isolated lumbricalis IV fibres were highly variable and thus represented more than one fibre type.
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PMID:Histochemical and physiological properties of Rana temporaria tibialis anterior and lumbricalis IV muscle fibres. 225 38

The thin filaments of the anterior byssus retractor muscle of the edible mussel Mytilus and the transluscent and opaque adductors of the oyster Crassostrea have been isolated and their properties investigated. We find that the thin filaments from all three muscles can activate skeletal muscle myosin ATPase in the presence of calcium but that the activity is inhibited in its absence. The filaments contain a protein which interacts with antibodies to vertebrate smooth muscle caldesmon on immunoblots. The antibodies relieve the inhibition of the thin-filament-activated myosin MgATPase. They can also bundle the thin filaments. We conclude that a caldesmon-like protein is present in molluscan muscle. As in the vertebrate smooth muscle, it could act as part of a control mechanism in addition to the myosin regulatory system. Vertebrate smooth muscle caldesmon can crosslink actin and myosin and it has been suggested that it may in this way contribute to the latch state. A similar interaction may be involved in the catch mechanism in molluscan muscle.
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PMID:Calcium regulated thin filaments from molluscan catch muscles contain a caldesmon-like regulatory protein. 225 39

The effect of temperature on the force-sarcomere velocity relation (20 degrees, 25 degrees, and 30 degrees C) and maximum velocity of sarcomere shortening (Vo; range 15 degrees-35 degrees C) was studied in trabeculae from rat heart. Sarcomere length and Vo were measured by laser diffraction techniques. Sarcomere length and sarcomere velocity, determined from each of the first-order diffraction lines, differed by less than 4%. Slack sarcomere length in the trabeculae appeared to be 1.9 microns. Isovelocity release techniques were used to obtain sarcomere velocity and Vo directly. Sarcomere velocity was measured at SL = 1.9-2.0 microns for elimination of contributions of parallel elastic force and restoring force to the external load of the sarcomeres. Peak twitch force development (Fo) was maximal (Fo-max) at 25 degrees C at [Ca2+]o = 1.5 mM. Lowering of the temperature below 25 degrees C led to development of spontaneous sarcomere activity and depression of Fo; both responses could be prevented by the addition of 0.5 mM procaine. Increase of temperature above 25 degrees C reduced twitch duration and Fo. Hill's rectangular hyperbola fitted the force-velocity data if the load during shortening was less than 70% of Fo. Vo appeared to be independent of the level of activation at all temperatures when Fo was maintained above 90% of Fo-max, either by an increase of [Ca2+]o (to 3.0 mM) or by paired pulse stimulation. Vo increased with increasing temperature; the parameter a, calculated from force-velocity relations measured at 20 degrees, 25 degrees, and 30 degrees C, decreased with increasing temperature. The Arrhenius plot of Vo was studied in detail over a wider temperature range (15 degrees-35 degrees C) and in smaller temperature increments. The relation was linear between 18 degrees and 33 degrees C; the observed Q10, defined as the ratio of Vo measured at temperature (T) over Vo at T-10 degrees C, was 4.6 A Q10 of 4.6 for Vo is consistent with the reported temperature dependence of rat cardiac actin-activated myosin ATPase, which suggests that the same reaction step may limit the activity of the enzyme in vitro and during shortening of the cardiac sarcomeres at zero external load.
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PMID:Force and velocity of sarcomere shortening in trabeculae from rat heart. Effects of temperature. 233 24

Calcium-dependent distance changes have been determined by resonance energy transfer in binary and ternary troponin complexes in order to collect evidence for the structural rearrangements which are part of the hypothetical trigger mechanism of skeletal muscle contraction. Donor and acceptor fluorophores were either intrinsic tryptophans in subunits with a favourable sequence from different species, quasi-intrinsic Tb3+ ions bound to troponin C or extrinsic labels attached to specific cysteine or methionine residues. All chemically modified subunits proved fully active in conferring calcium sensitivity onto myosin ATPase. Nine distances were determined between five sites which allowed construction of a three-dimensional lattice representing the spatial distribution of four sites in the ternary complex of troponin C, I and T. Distances in binary complexes were nearly unaltered upon addition of the third subunit. Regulatory calcium binding caused distance changes of the order of 0.7-1.1 nm. In view of the large displacements of the hypothetical mechanism, they turned out to be smaller than anticipated. The fluorophoric sites selected may be localized in a zone of the troponin complex which happens to be relatively little affected by the mechanism. Alternatively, amplification of the moderate changes seen here would require the complete set of thin filament proteins.
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PMID:Calcium-dependent distance changes in binary and ternary complexes of troponin. 235 Nov 40


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