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 Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, we conclude that altered protein metabolism may be an important primary factor in the genesis of heart failure.
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PMID:The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure. 13 12

The role of subcellular alterations in the process of heart failure remains ill-defined. Because contractile performance of failing heart muscle is depressed, possible alterations in the myosin molecule could be of particular relevance. There is increasing evidence that myofibrillar ATPase activity is reduced in congestive heart failure, whereas the findings on myosin ATPase are still controversial. The molecular causes of the reduced activity are currently not known. Because alpha-MHC is present only in small amounts in normal ventricles, a shift in favor of beta-MHC is of minor importance. Also immunohistochemical data on subspecies of beta-MHC seem not to provide an explanation. A new type of myosin heterogeneity was found by optimizing native polyacrylamide gel electrophoresis in the presence of pyrophosphate. Two bands (VA and VB) were observed in ventricles of patients with valvular disease. Because the two bands were detected also in normal hearts of large mammals, the existence of VA/VB cannot be diagnostic of diseased heart. However, the VA/VB ratio was influenced by the hemodynamic load, whereby the fast migrating band (VA) increased with the diastolic and systolic load. Because a relationship with the hemodynamic load was observed only in surgical muscle specimens, it appears that this heterogeneity is prone to post mortem modification. Further work is required to identify the molecular nature of this heterogeneity and to examine the therapeutic potential of a pharmacological modification of the VA/VB ratio.
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PMID:Structural and functional diversity of human ventricular myosin. 138 32

After myocardial infarction in rats, muscle performance in the remaining hypertrophied myocardium deteriorates and is associated with a decrease in myosin adenosinetriphosphatase (ATPase) activity and a shift to the V3 myosin heavy-chain isoform. We have previously shown in another model of hypertrophy, secondary to renovascular hypertension, that chronic intermittent adrenergic stimulation with dobutamine (Db) can prevent this biochemical adaptation. The present study was undertaken to assess the effects of chronic Db treatment on cardiac mass, function, metabolism, and myosin biochemistry in animals subjected to chronic myocardial infarction. Four groups of rats were studied: controls, animals treated with Db (2 mg/kg 2X daily for 4 wk), animals subjected to myocardial infarction and killed after 4 wk (MI), and MI animals concurrently treated with Db for 4 wk (MI-Db). The two MI groups were subdivided into those with and without congestive heart failure (CHF). Heart weight was increased by 13% with Db, unchanged in the infarct groups without CHF, and increased by 9 and 22% in the infarct groups with CHF. Db did not have any additional effect on heart weight in these later groups. Infarct weight was greatest in the animals with CHF, and viable myocardium was equivalent in all infarct groups suggesting that CHF was associated with a greater degree of hypertrophy. Ventricular performance, as assessed in an isovolumic heart apparatus, was markedly depressed in both infarct groups with CHF and was not affected by Db. Db increased myosin ATPase activity in control and infarcted animals both with and without congestive heart failure. Myosin oxygen consumption and lactate production were not adversely affected by Db.
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PMID:Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats. 199 90

Left ventricular papillary muscle function, transmembrane action potentials, myosin adenosinetriphosphatase (ATPase) and isoenzyme distribution, and myocardial pathology were studied in hypertensive (H), diabetic (D), hypertensive-diabetic (HD), and control (C) rats. There was approximately 50% relative left ventricular hypertrophy in H and HD rats. Relative lung and liver weights were greater in HD rats. Peak velocity of shortening tended to decrease progressively in H, D, and HD rats. The duration of contraction and relaxation was markedly prolonged in Ds and HDs. The length-developed tension relation was blunted in HDs. The negative inotropic effect of verapamil was similar in all groups. Resting membrane potential and amplitude were decreased in D and HD rats. Action potential duration was increased in H, D, and especially HD rats. The shortening of action potential duration with increased stimulus frequency was greater in H, D, and especially HD rats than in Cs. Left ventricular myosin ATPase and V1 isoenzyme content decreased progressively in H, D, and HD rats. Right ventricular V1 isoenzyme content was not affected in H rats but was markedly decreased in D and HD rats. Left (and right) ventricular pathology was unchanged in rats with diabetes but was increased in rats with hypertension. These data suggest that the combination of myocardial pathology (due to hypertension) and cellular dysfunction (caused mainly by diabetes) may result in cardiomyopathy and congestive heart failure in the HD rat.
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PMID:Hypertensive-diabetic cardiomyopathy in rats. 213 24

Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years. Pathological studies show left ventricular hypertrophy and fibrosis with varying degrees of small vessel disease, the functional significance of which is uncertain. Hypertension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterization, in patients symptomatic of heart failure, either congestive or restrictive patterns have been observed. In contrast, asymptomatic diabetics had decreased left ventricular compliance but normal systolic function on hemodynamic study. Noninvasive studies show alterations in systolic and especially diastolic function, particularly in diabetics with microvascular complications and/or coexistent hypertension. Using load-independent measures of contractility, however, systolic function was generally found to be normal in asymptomatic normotensive diabetics. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and increased interstitial connective tissue were observed in chronically diabetic dogs. In contrast, ventricular myocardium from diabetic rats exhibits a reversible decrease in the speed of contraction, prolongation of contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzyme distribution, alterations in a variety of Ca2+ fluxes, and changes in responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohydrate, lipid, and adenine nucleotide metabolism in the diabetic heart.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetic cardiomyopathy. 808 30

Crossbridge (CB) properties were investigated in isolated diaphragm of rabbits during congestive heart failure (CHF, n=9) induced by chronic volume and pressure overload. This model induced cardiac hypertrophy and heart failure. Controls (C) were prepared (n=14). Compared to C, peak tension in CHF fell by 57% in twitch and by 40% in tetanus; Vmax declined by 47% in twitch and by 48% in tetanus. Our study provided an analytical means of calculating from A. F. Huxley's equations the rate constants for CB attachment and detachment, CB single force (II), CB number per mm3 (m'), peak mechanical efficiency (Effmax), and turnover rate of myosin ATPase (kcat); m', II, and Effmax were lower in CHF than in C in both twitch and tetanus. The marked decline in m' and II accounted for the fall in diaphragm strength. In the overall population of C and CHF, Effmax was linearly related to II. Conversely, there was no relationship between Vmax and kcat. Dissociation between Vmax and kcat might be explained by the crucial role attributed to two apparently nonconserved surface 'loops' on the motor domain of myosin head.
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PMID:Mechanics, energetics, and crossbridge kinetics of rabbit diaphragm during congestive heart failure. 970 70

Ca(2+) is well known as the central player in cardiac cell physiology, mediating Ca(2+) activation of myosin ATPase and contraction, the stimulation of Ca(2+)-activated signaling pathways and modulation of mitochondrial energy production. Abnormalities of Ca(2+) handling are a well-studied mechanism of decompensation in heart failure. Less appreciated is the role of cytosolic Na(+) (Na(i) (+)), which can dramatically influence the transfer rates and distribution of Ca(2+) among the intracellular compartments of the myocyte. Since Na(i) (+) can vary widely under different physiological and pathological conditions, and its effects depend on multiple ion gradients and membrane electrical potentials, unraveling the global influence of Na(i) (+) on cell function is complex, requiring an integrative view of cardiomyocyte physiology. Here, we discuss how abnormal Na(i) (+) regulation not only influences the cytosolic Ca(2+) transient and the cellular action potential but also alters mitochondrial Ca(2+) uptake and the balance of energy supply and demand of the cardiomyocyte, which may contribute to oxidative stress and cardiac decompensation. The implications for sudden cardiac death and the potential for novel therapeutic interventions are discussed.
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PMID:The role of Na dysregulation in cardiac disease and how it impacts electrophysiology. 1865 Sep 59