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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to identify defects in Na+-Ca2+ exchange and Ca2+-pump systems in cardiomyopathic hearts, the activities of sarcolemmal Na+-dependent Ca2+ uptake, Na+-induced Ca2+ release, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase were examined by employing cardiomyopathic hamsters (UM-X7.1) and catecholamine-induced cardiomyopathy produced by injecting isoproterenol into rats. The rates of Na+-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities of sarcolemmal vesicles from genetically-linked cardiomyopathic as well as catecholamine-induced cardiomyopathic hearts were decreased without any changes in Na+-induced Ca2+-release. Similar results were obtained in Ca2+-paradox when isolated rat hearts were perfused for 5 min with a medium containing 1.25 mM Ca2+ following a 5 min perfusion with Ca2+-free medium. Although a 2 min reperfusion of the Ca2+-free perfused hearts depressed sarcolemmal Ca2+-pump activities without any changes in Na+-induced Ca2+-release, Na+-dependent Ca2+ uptake was increased. These results indicate that alterations in the sarcolemmal Ca2+-efflux mechanisms may play an important role in cardiomyopathies associated with the development of intracellular Ca2+ overload.
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PMID:Sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities in cardiomyopathies due to intracellular Ca2+-overload. 297 15

Diabetes was introduced in rats by an intravenous injection of streptozotocin (65 mg/kg). Animals were sacrificed 8 weeks later and mitochondria were isolated from the ventricular tissue by differential centrifugation. The state 3 respiration, oxidative phosphorylation rate and Mg2+-dependent ATPase activities were depressed in mitochondria from diabetic hearts. These changes were partially reversible upon 2 weeks of insulin and fully reversible after 4 weeks of insulin therapy. Mitochondrial calcium uptake but not calcium binding, was decreased in diabetes and this change was fully reversible by 2 weeks of insulin administration. The observed alterations in mitochondrial function could not be explained on the basis of any changes in mitochondrial lipid and protein composition or subcellular contamination. These results indicate the presence of a generalized depression in mitochondrial function in chronic diabetes and such a defect is suggested to contribute in the development of cardiomyopathy at late stages of diabetes.
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PMID:Heart mitochondrial function in chronic experimental diabetes in rats. 299 24

The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (P less than 0.05) in sarcoplasmic reticulum Ca2+, K+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (P less than 0.01) and glutathione (P less than 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (P less than 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (P less than 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity.
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PMID:Adriamycin cardiomyopathy: implications of cellular changes in a canine model with mild impairment of left ventricular function. 299 97

The UM-X7.1 myopathic and control hamsters at 40, 120 and 280 days of age were employed for the examination of heart sarcolemmal Ca2+-transport activities. Na+-dependent Ca2+ uptake activities were significantly depressed in myopathic animals at 120 and 280 days of age in comparison to the control values. No difference in Na+-induced Ca2+ release activities was found between control and experimental sarcolemmal vesicles. ATP-dependent Ca2+ binding and Ca2+-stimulated, Mg2+ ATPase activities were depressed in the experimental animals at 120 and 280 days of age. Similar alterations in the sarcolemmal Na+-dependent Ca2+ exchange and Ca2+-pump activities were seen upon treating the control hamsters with 40 mg/kg isoproterenol for 24 hr. It is suggested that a depression in the sarcolemmal Ca2+ transport activities may contribute to the development of intracellular Ca2+ overload in the genetically determined cardiomyopathy in hamsters and such a defect may be due to excessive amount circulating catecholamines in these animals.
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PMID:Sarcolemmal Na+-Ca2+ exchange during the development of genetically determined cardiomyopathy. 300 47

The hamster hereditary cardiomyopathy provides a unique model for the study of membrane abnormalities during chronic congestive heart failure. It is associated with intracellular calcium accumulation, mitochondrial calcification and cell necrosis. Previous studies have shown a decrease in Na,K-ATPase activity purified from ventricle sarcolemma. The present study demonstrates a decrease in K-dependent 3-O-methylfluorescein phosphatase (3-O-MFPase) activity from 1.93 to 1.30 mumol/g wet wt. or 33% in crude homogenates from the left ventricle of 7-months-old cardiomyopathic hamsters as compared to control animals. This represents an equivalent decrease in Na, K-ATPase activity. The values are several times higher than previously published for membrane fractions of myocardium from the hamster. Concomitantly, there was an increase in intracellular Na-concentration of the myocardium of 42% whereas the K-concentration was unchanged. The decrease in Na,K-pump concentration may be of importance for the increase in intracellular sodium and ensuing calcifying necrosis observed in the myocardium of cardiomyopathic hamsters. It is emphasized that quantification of the Na,K-ATPase or Na,K-pump should preferably be performed using crude homogenates.
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PMID:Heart Na,K-ATPase activity in cardiomyopathic hamsters as estimated from K-dependent 3-O-MFPase activity in crude homogenates. 304 Oct 9

The isometric twitch properties of papillary muscles from hearts of 30- to 53-day-old cardiomyopathic hamsters (BIO 14.6) were studied before and after exposure to the cardiac glycoside, ouabain. The diseased tissue was weakly responsive to ouabain (3 to 100 microM), as compared to a more appreciable positive inotropic response in papillary muscle of similarly aged normal hamsters (BIO F1B). These data suggest that the activity of Na+,K+-ATPase is attenuated in the diseased sarcolemma. Pretreatment with the beta-adrenoceptor agonist, isoproterenol (0.1 microM), slightly increased the sensitivity of normal muscle to ouabain, however the response of myopathic muscle was greatly enhanced. These findings may be of significance to the genesis of cellular calcium overload hypothesized to be involved in the necrosis and degeneration of heart cells in this animal model of genetic cardiomyopathy.
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PMID:The effect of ouabain on hearts of cardiomyopathic hamsters: potentiation by isoproterenol. 362 90

In earlier studies using papillary muscles of the rat left ventricle and highly sensitive thermopiles we demonstrated that the heat liberated per gram of myocardium per unit of developed tension-time integral is decreased when the rats suffered from hypothyroidism or renal hypertension. This increase in economy of force production was shown to be associated with a decrease in myosin-ATPase activity and a change in isomyosin composition. In a recent study we showed an increase in heat per gram of mammalian myocardium per tension-time integral of 70% after application of isoproterenol. In order to study the relationship between energy costs and developed tension-time integral in the human heart, haemodynamics and myocardial oxygen consumption were measured. The data were obtained using a Millar microtip catheter pressure transducer and the argon method. Haemodynamics and myocardial energetics were analysed in 8 patients without significant heart disease before and after application of isoproterenol and in 10 patients with dilative cardiomyopathy (NYHA II-III). During one cardiac cycle, myocardial oxygen consumption per gram of LV myocardium per beat (MVO2/g x beat) is related to LV stress-time integral (integral of sigma xt). The economy of myocardial contraction (EC) was calculated by (formula; see text) EC was 11.3 +/- 3.2 in normal and 14.3 +/- 4.7 dyn x s x g/cm2 x mu cal in dilative cardiomyopathic hearts (NS). Isoproterenol decreased EC from 11.3 +/- 3.2 to 5.5 +/- 1.6 dyn x s x g/cm2 x mu cal in the normal hearts (p less than 0.01). In the rat myocardium, changes in economy of force generation were found due to catecholamines, pressure overload and hypothyroidism. In the human heart, similar energetic changes were observed due to catecholamines. No significant differences in energy of force production were seen between normal and dilative cardiomyopathic hearts. The effect of catecholamines in the mammalian and human myocardium is explained by changes in activation processes and in chemomechanical energy transduction at the level of the contractile proteins.
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PMID:Acute and chronic changes of myocardial energetics in the mammalian and human heart. 366 28

The purpose of this study was to identify alterations in specific enzyme and Ca2+ binding activities in cardiac sarcolemmal fractions from UM-X7.1 myopathic Syrian hamsters during the development of cardiomyopathy. Experimental and healthy control animals were examined from 25 to 200 days of age. Sarcolemmal Na+, K+-ATPase activity was depressed in the myopathic hamsters throughout the time course of this study. Sarcolemmal ATP-independent Ca2+ binding was found to be depressed in experimental animals as early as 55 days of age. Ca2+ -stimulated, Mg2+ -dependent ATPase activity was depressed in the experimental animals by 90 days of age and this decrease in enzyme activity was accompanied by a decrease in ATP-dependent Ca2+ binding capacity of the sarcolemmal membranes. Mg2+ -ATPase and Ca2+ -ATPase activities were only affected in the latter stages of the disease (155 to 200 days old). NaF, epinephrine and Gpp(NH)p stimulation of the sarcolemmal adenylate cyclase activity was also observed to be attenuated during the latter stages of the disease. These defects in adenylate cyclase system of the sarcolemmal fraction appeared specific since basal adenylate cyclase activity was not altered at any age studied. The results demonstrate that the earliest lesions in sarcolemmal activity in myopathic hamster heart occur in Na+, K+-ATPase and ATP-independent Ca2+ binding capacity. These defects correspond temporally to the initial stages of cardiac necrotic development in this strain of myopathic hamster.
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PMID:Sarcolemmal alterations during the development of genetically determined cardiomyopathy. 614 91

Previous reports have documented a cardiomyopathy in rats resulting from streptozotocin-induced diabetes. In order to determine the reversibility of streptozotocin-induced cardiomyopathy to insulin therapy, hearts from rats made diabetic by streptozotocin for 6 weeks and then treated with insulin for 3 weeks were compared with untreated diabetic rats and control rats not injected with streptozotocin. When perfused in an isolated working heart apparatus with 5.5 mM glucose as substrate, hearts from untreated diabetic rats when compared to hearts from either streptozotocin-injected rats treated with insulin or control rats showed significant depressions in peak left ventricular pressure, maximal positive and negative dP/dt, oxygen extraction, lactate production and effluent lactate; pyruvate ratio. Ca2+-actomyosin ATPase was also depressed in untreated diabetics. As left atrial pressure was raised in untreated diabetic rats, a decline in cardiac output was observed, whereas in insulin-treated or control groups there was no such negative response. Indices of cardiac performance were significantly greater in insulin-treated rats when compared to control rats suggesting overcorrection with insulin therapy. To explore whether insulin treatment may have a beneficial effect on the myocardium control rats were made hyperinsulinemic for 6 to 7 weeks. Shorter isovolumic relaxation times and elevated values for Ca2+-actomyosin ATPase were observed in hearts from hyperinsulinemic animals when compared to hearts from control animals. These results demonstrate complete reversibility of streptozotocin-induced cardiomyopathy and confirm that this condition is due to insulin deficiency and not to a primary cardiotoxic effect of streptozotocin.
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PMID:Left ventricular function after chronic insulin treatment in diabetic and normal rats. 622 76

Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female with an obstructive cardiomyopathy. The specificity of 15 monoclonal antibodies to myosin heavy chains was assessed by the reactivity of muscle extracts and of chymotryptic myosin fragments of different sizes with these antibodies, as determined by the immune replicate technique; some of the monoclonal antibodies cross-reacted only with the ventricular V3-type myosin from hypothyroid rats, whereas the other antibodies cross-reacted both with the latter and with the ventricular V1-type myosins from normal young rats. Immunological heterogeneity of the fibers from human atrial muscles and from human ventricular muscles was detected by some of the antimyosin antibodies by means of indirect immunofluorescence. Histochemical fiber heterogeneity was also detected by adenosine triphosphatase staining of the same tissues. Because of the close correspondence observed between the immunological and histochemical responses of atrial fibers, it has been postulated that at least two distinct types of myosin exist in the human atrium, each myosin form being histochemically related to either alpha- or beta-like ventricular myosin heavy chains. In contrast, there was no direct correspondence between the two experimental approaches in human ventricles, and it is postulated that at least three distinct types of myosin exist within the human ventricles, one V1-type myosin, presumably corresponding to the very rare fibers with an alkaline-stable adenosine triphosphatase activity, and two other V3-type myosins corresponding to immunologically different fibers, each having an alkaline-labile adenosine triphosphatase activity. Monoclonal antibodies that can distinguish among the different myosin variants were further used to provide the basis for an anatomical description of fiber types and myosin types within the human atrial and ventricular myocardium in the whole hearts of two young boys who died sudden violent deaths. Small zones of myosin variation were seen to be scattered, but probably not randomly distributed, within large areas of myocardium in which the cellular distribution of myosin was constant; the large areas had one myosin distribution specific for each cardiac cavity. No clear-cut conclusions can yet be made concerning the physiological role of the regional variations observed in the distribution of the different molecular forms of myosin.
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PMID:Fiber types and myosin types in human atrial and ventricular myocardium. An anatomical description. 623 24


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