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Query: UNIPROT:P06889 (Mol)
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C-protein, a component of the thick filaments of striated muscles, is reversibly phosphorylated and dephosphorylated in heart. It has been hypothesized that C-protein may be involved in regulating contraction, because the extent of C-protein phosphorylation correlates with the rate of cardiac relaxation. To test this hypothesis, the effects of phosphorylated and unphosphorylated C-protein on the actin-activated ATPase activity of myosin filaments prepared from DEAE-Sephadex-purified myosin were examined. Unphosphorylated C-protein (0.1 microM to 1.5 microM) stimulated actin-activated myosin ATPase activity in a dose-dependent manner. With a myosin: C-protein molar ratio of approximately 1, actin-activated myosin ATPase activity was elevated up to 3.2 times that of the control. Phosphorylated C-protein (2.5 mol PO4/mol C-protein) stimulated the activity somewhat less (2.5 times that of control). The stimulation of ATPase activity by C-protein was due to an increase in the Vmax value (from 0.25/second to 0.62/second) and a decrease in the Km value (from 11.9 microM to 6.7 microM). The addition of C-protein to actomyosin solutions produced an increase in the light-scattering of the actomyosin solution and a distinct precipitation of the actomyosin with time. Phosphorylated C-protein had a smaller effect on light-scattering than dephosphorylated C-protein. C-protein had a negligible effect on Ca-ATPase, EDTA-K-ATPase, or Mg-ATPase activities in the absence of actin. C-protein had only small effects on the actin-activated ATPase of heavy meromyosin. These results suggest that C-protein stimulates actin-activated myosin ATPase activity by enhancing the formation of stable aggregates between actin and myosin filaments.
J Mol Biol 1985 Nov 05
PMID:Effects of phosphorylated and unphosphorylated C-protein on cardiac actomyosin ATPase. 293 53

We measured the interrelationships between ventricular muscle myosin mass, myosin ATPase activity and collagen in cats with varying degrees of hypertrophy from left ventricular (LV) pressure-overload produced by either aortic banding or renal hypertension. In order to compare two models of LV pressure-overload with different time courses of progression, the results were analyzed as a function of LV mass or LV weight/body weight (LV/BW) ratio. Myosin was quantitated by SDS-polyacrylamide gel electrophoresis and hydroxyproline was measured as an index of collagen. Myosin concentration was positively correlated with increasing LV mass in control cats. However, in pressure-overloaded LV, myosin concentration was elevated and nearly constant for LV less than 9.0 g, but decreased in LV greater than 9.0 g. Myosin concentration in pressure-overloaded LV was greatest before a significant increase in LV/BW ratio. Hydroxyproline concentration was inversely related to myosin concentration in both LV pressure-overload models and increased with the severity of hypertrophy. Actomyosin ATPase activity in pressure-overloaded LV, was not significantly different from control over a wide range of LV/BW ratios. However, absolute myosin ATP hydrolysis in pressure-overloaded LV, increased by as much as 40%, relative to control, due primarily to increased myosin. The changing spectrum and interrelationships of myosin and collagen were independent of the mechanism of pressure-overload, but were correlated with the severity of hypertrophy.
J Mol Cell Cardiol 1987 Jan
PMID:Myocardial changes during the progression of left ventricular pressure-overload by renal hypertension or aortic constriction: myosin, myosin ATPase and collagen. 295 26

Heterotopic cardiac transplants are vascularly perfused organs that can be used to study the regulation of myocardial protein content. Prior studies have demonstrated that cardiac isografts undergo marked atrophy with a decrease in weight and myosin content. In the present studies we have investigated the changes in size, myosin content and myosin isoenzyme distribution in the heterotopic cardiac allografts. Six days after transplantation allograft hearts were not spontaneously beating and histologically showed evidence of necrosis and cellular infiltration. Total heart weight (816 +/- 16 mg) and protein content (117 +/- 7 mg) were significantly greater in the allografts compared to in situ hearts (471 +/- 11 and 90 +/- 5 mg respectively, (P less than 0.01). In contrast to the increase in weight there was a simultaneous decrease in myosin ATPase (26%), the V1 isoform of the myosin isoenzyme (43%), and myosin content (53%) in the allograft heart. These studies demonstrate that similar to cardiac isografts, allograft hearts undergo a decrease in myosin content and a shift in myosin isoenzymes. In contrast to the marked atrophy of the cardiac isograft, the allograft heart weight is increased most likely due to rejection with cellular infiltration and an increased water content.
J Mol Cell Cardiol 1987 Sep
PMID:Myosin content and myosin isoenzyme distribution in the heterotopic rat heart allograft. 296 35

In order to gain some information regarding Ca2+-dependent ATPase, the enzyme was purified from cardiac sarcolemma and its properties were compared with Ca2+-ATPase activity of myosin purified from rat heart. Both Ca2+-dependent ATPase and myosin ATPase were stimulated by Ca2+ but the maximal activation of Ca2+-dependent ATPase required 4 mM Ca2+ whereas that of myosin ATPase required 10 mM Ca2+. These ATPases were also activated by other divalent cations in the order of Ca2+ greater than Mn2+ greater than Sr2+ greater than Br2+ greater than Mg2+; however, there was a marked difference in the pattern of their activation by these cations. Unlike the myosin ATPase, the ATP hydrolysis by Ca2+-dependent ATPase was not activated by actin. The pH optima of Ca2+-dependent ATPase and myosin ATPase were 9.5 and 6.5 respectively. Na+ markedly inhibited Ca2+-dependent ATPase but had no effect on the myosin ATPase activity. N-ethylmaleimide inhibited Ca2+-dependent ATPase more than myosin ATPase whereas the inhibitory effect of vanadate was more on myosin ATPase than Ca2+-dependent ATPase. Both Ca2+-dependent ATPase and myosin ATPase were stimulated by K-EDTA and NH4-EDTA. When myofibrils were treated with trypsin and passed through columns similar to those used for purifying Ca2+-ATPase from sarcolemma, an enzyme with ATPase activity was obtained. This myofibrillar ATPase was maximally activated at 3-4 mM Ca2+ and 3 to 4 mM ATP like sarcolemmal Ca2+-dependent ATPase. K+ stimulated both ATPase activities in the absence of Ca2+ and inhibited in the presence of Ca2+. Both enzymes were inhibited by Na+, Mg2+, La3+, and azide similarly. However, Ca2+ ATPase from myofibrils showed three peptide bands in SDS polyacrylamide gel electrophoresis whereas Ca2+ ATPase from sarcolemma contained only two bands. Sarcolemmal Ca2+-ATPase had two affinity sites for ATP (0.012 mM and 0.23 mM) while myofibrillar Ca2+-ATPase had only one affinity site (0.34 mM). Myofibrillar Ca2+-ATPase was more sensitive to maleic anhydride and iodoacetamide than sarcolemmal Ca2+-ATPase. These observations suggest that Ca2+-dependent ATPase may be a myosin like protein in the heart sarcolemma and is unlikely to be a tryptic fragment of myosin present in the myofibrils.
Mol Cell Biochem 1987 Oct
PMID:A comparative study of the rat heart sarcolemmal Ca2+-dependent ATPase and myosin ATPase. 296 55

Dietary manipulations involving high carbohydrate feeding increase V1 cardiac myosin isoform expression in hormonally deficient rats. The purpose of this study was to determine if extremes in dietary carbohydrate availability could alter cardiac myosin isoform patterns in normal weanling and adult rats. Three and six weeks of dietary manipulations (either high or low carbohydrate diets) failed to change calcium-activated myofibril ATPase activity, calcium regulated myofibril ATPase activity, or the myosin isoform distribution in the adult. In contrast, a four week, high carbohydrate diet reduced calcium activated myosin ATPase activity by 33%, calcium regulated myofibril ATPase activity by 10%, and V1 isoform expression by 66% in weanling rats. Although the low carbohydrate diet caused no change in the myosin ATPase properties, it decreased V1 isoform expression by 17%. These results show that carbohydrate availability can alter cardiac myosin isoform expression in normal rats, but only at weanling age. The reason for this age-related contrast in response to dietary manipulations is unknown at this stage. The dietary manipulations may have acted directly on the heart by creating a state of malnutrition, or indirectly, by altering some developmental process which links maturation of the sympathetic nervous system with myosin isoform expression.
Mol Cell Biochem 1987 Dec
PMID:Differential effects of carbohydrate intake on cardiac myosin isoform expression in normal weanling and adult rats. 296 58

Control of mitochondrial respiration depends on ADP availability to the F1-ATPase. An electrochemical gradient of ADP and ATP across the mitochondrial inner membrane is maintained by the adenine nucleotide translocase which provides ADP to the matrix for ATP synthesis and ATP for energy-dependent processes in the cytosol. Mitochondrial respiration is responsive to the cytosolic phosphorylation potential, ATP/ADP.Pi which is in apparent equilibrium with the first two sites in the electron transport chain. Conventional measures of free adenine nucleotides is a confounding issue in determining cytosolic and mitochondrial phosphorylation potentials. The advent of phosphorus-31 nuclear magnetic resonance (P-31 NMR) allows the determination of intracellular free concentrations of ATP, creatine-P and Pi in perfused muscle in situ. In the glucose-perfused heart, there is an absence of correlation between the cytosolic phosphorylation potential as determined by P-31 NMR and cardiac oxygen consumption over a range of work loads. These data suggest that contractile work leads to increased generation of mitochondrial NADH so that ATP production keeps pace with myosin ATPase activity. The mechanism of increased ATP synthesis is referred to as 'stimulus-response-metabolism' coupling. In muscle, increased contractility is a result of interventions which increase cytosolic free Ca2+ concentrations. The Ca2+ signal thus generated increases glycogen breakdown and myosin ATPase in the cytosol. This signal is concomitantly transmitted to the mitochondria which respond to small increases in matrix Ca2+ by activation of Ca2+-sensitive dehydrogenases. The Ca2+-activated dehydrogenase activities are key rate-controlling enzymes in tricarboxylic acid cycle flux, and their activation by Ca2+ leads to increased pyridine nucleotide reduction and oxidative phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1988 Jun
PMID:Control of mitochondrial respiration in muscle. 305 Apr 50

Hearts of genetically myopathic male hamsters (BIO 53 : 58) were studied at 1 month, 2 months, 3 months, 4 to 5 months and 7 months of age. The time course of alterations in the cardiac myofibrillar ATPase activity, the relationship of myofibrillar ATPase activity to free [Ca2+], myosin ATPase activity and the distribution of heavy chain myosin isoenzymes were evaluated. Mg2+-Ca2+ ATPase activity of cardiac myofibrils in myopathics was increased in 4 month and 7 month-old hamsters. Elevated Mg2+ ATPase activity was found as early as in 2-month-old hamster. However, there was no loss in the regulation of the myopathic myofibrillar assembly as measured by the PCa response (10(-7) M to 10(-4) M Ca2+). Scans of SDS electrophoresis slab gels of cardiac myofibrillar proteins from control (C) and myopathic animals (M) did not show any differences at any age group (1, 4 and 7 months). There was a significant decrease in myosin Ca2+ ATPase activity and actin activated Mg2+-ATPase activity at 4 to 5 months and 7 months of age in the myopathic hearts. At all ages in normal and myopathic animals cardiac myosin consisted of three isoenzymes, V1, V2 and V3. At all ages in controls and at 1 to 3 months in myopathics, V1 predominated and the isoenzyme distribution was V1 greater than V2 greater than V3. However, in myopathics at 4 to 5 months, the distribution was V1 = V3 greater than V2 and at 7 months was V3 greater than V2 greater than V1. Our experiments suggest alterations in different components of the contractile protein system that occur at different stages of myopathy.
J Mol Cell Cardiol 1985 Feb
PMID:Multiple cardiac contractile protein abnormalities in myopathic Syrian hamsters (BIO 53 : 58). 315 46

Myosin from chicken pectoralis muscle consists of isozymes that differ in their alkali light chains. It is possible to isolate alkali 1 (A1) and alkali 2 (A2) homodimers of native myosin by immunoadsorption methods, and to compare their steady-state kinetics as well as their assembly into synthetic filaments under a variety of ionic conditions. Bipolar filaments of the isozymes formed at low salt concentrations had a narrow length distribution and did not differ from controls made from unfractionated myosin. Chicken myosin also assembles into highly homogeneous minifilaments similar to those formed by rabbit myosin in a citrate/Tris buffer. Analytical ultracentrifugation and electron microscopy showed that A1-homodimer, A2-homodimer and unfractionated myosin assembled into 0.3 micron short, bipolar minifilaments, which were indistinguishable from one another in size and shape. The steady-state myosin ATPase activity of the two homodimeric isozymes was identical in K+(EDTA) and Ca2+ assay media. The actomyosin Mg2+ ATPase measured at 25 and 55 mM-KCl (pH 8.0) showed only minor differences in both Vmax and Kapp. Actomyosin activity was also determined for the more homogeneous minifilament preparations of the isozymes and these, as well, produced essentially indistinguishable kinetic parameters. Thus we find no evidence to support the hypothesis that a particular alkali light chain of myosin can affect either the structure of the filaments or the steady-state rate of ATP hydrolysis.
J Mol Biol 1983 Oct 25
PMID:Assembly and kinetic properties of myosin light chain isozymes from fast skeletal muscle. 622 5

It has been recognized for a long time that changes in hormone secretion can influence cardiac function; however, the biochemical basis for these changes has only recently been clarified. In this review the influences of hormonal status on the contractile protein myosin is discussed. Myosin has a rod-like portion and a globular head and consists of two myosin heavy chains (MHC) and four light chains (LC), two of which are identical. The globular head is the site of an ATP-splitting enzyme, the myosin ATPase, and increases in myosin ATPase activity are closely related to an increased velocity of contraction of the heart. Myosin ATPase activity shows marked response to alterations in thyroid hormone, insulin, glucocorticoid, testosterone and catecholamine levels, but marked animal species differences in this response occur. Thyroid hormone administration to normal rabbits, for example, increases myosin ATPase activity markedly, but the myosin ATPase activity of hyperthyroid rats remains unchanged. In contrast, in hypothyroid rats myosin ATPase activity is markedly decreased but the hypothyroid rabbit shows no such response. These species-related differences in the hormonal response of myosin ATPase activity result from the predominance pattern of specific myosin isoenzymes. In the normal rat heart three myosin isoenzymes, V1, V2 and V3, can be separated electrophoretically. Myosin V1 predominates (70% of total myosin), and has the highest myosin ATPase activity, whereas in rabbits myosin V3, which has a lower myosin ATPase activity, is the predominant isomyosin. Thyroid hormone administration to rabbits induces myosin V1 predominance and therefore increases myosin ATPase activity, whereas in hyperthyroid rats only a small further increase in V1 predominance can occur. The alterations in myosin isoenzyme predominance and myosin ATPase activity are closely correlated to changes in cardiac contractility. Hormone-induced alterations in myosin isoenzyme predominance are mediated through changes in the formation of two isoforms of myosin heavy chain. Changes in the expression of different myosin heavy chain genes are most likely responsible for the thyroid hormone and insulin-induced alterations in myosin isoenzyme predominance. Investigation of the control of myosin heavy chain formation can provide further insights into the hormonal control of a multigene family as well as broaden our understanding of the molecular events which result in altered cardiac contractility.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Endocrinol 1984 Mar
PMID:Hormonal influences on cardiac myosin ATPase activity and myosin isoenzyme distribution. 623 63

The decrease in myosin ATPase activity observed in cardiac hypertrophy induced by cardiac overload has been related to an isoenzymic redistribution of myosin. To test the hypothesis of an additional regulation of myosin ATPase through light chain phosphorylation, we measured the myosin kinase activity together in sham-operated and 50% to 100% hypertrophied rat hearts. The myosin kinase were purified approximately 600 fold with 6% yield by ion exchange chromatography and calmodulin-affinity chromatography. The presence of very important levels of proteolytic activity in the rat heart resulted in a partial loss of the myosin kinase calmodulin-dependency. The major component from both myosin kinase purified fractions was a 63 kdaltons protein. The protein content was identical in myosin kinase purified fractions from sham-operated and hypertrophied hearts. The calmodulin-dependent activity of myosin kinase, assayed in the presence of 0.1 mM Ca2+ and 10(-6) M calmodulin (about 6.6 nmol P X min-1 X mg-1), was identical in sham-operated and 50% to 100% hypertrophied hearts. Thus, myosin kinase specific activity, in these conditions, was unchanged in rat heart chronic hypertrophy. This result suggests that no direct functional relationship exists between the enzymatic properties of myosin and myosin kinase during the chronic phase of cardiac hypertrophy.
J Mol Cell Cardiol 1984 Nov
PMID:Unchanged myosin kinase activity in hypertrophied rat heart. 624 May 42


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