Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronic treatment of spontaneously hypertensive rats (SHR) with 7,8-dimethyl-10-(3-chlorobenzyl) isoalloxazine [CBI], 7,8-diethyl-10-aminol isoalloxazine [DEAI], enduron (methyclothiazide) and amiloride were studied for their effects on blood pressure and cardiac contractile protein ATPase activities. After 35 weeks of treatment all the above antihypertensive agents showed a decrease in blood pressure in the SHR (p less than 0.01). Chronic treatment with CBI, DEAI, enduron, and amiloride significantly improved the myofibrillar ATPase activity at all pCa2+ concentrations (p less than 0.01). Furthermore, CBI, DEAI, enduron, and amiloride drug treatments enhanced actin-activated myosin ATPase activity (p less than 0.01). The Ca2(+)-activated myosin ATPase activity was significantly elevated after treating with CBI and DEAI (p less than 0.01). These results suggest that the antihypertensive agents used in this study helped in reducing the blood pressure with a subsequent increase in myocardial contractile protein ATPase activity.
Basic Res Cardiol
PMID:Effects of riboflavin analogues and diuretics on the spontaneously hypertensive rat heart. 214 69

In an attempt to clarify the mechanism of sarcoplasmic reticulum (SR) dysfunction during the genesis of irreversible damage in the ischemic-reperfused myocardium, the changes in SR Ca2(+)-pumping ATPase (Ca2(+)-activated, Mg2(+)-dependent ATPase; Ca2(+)-ATPase) activity were studied during ischemia and subsequent reperfusion in the isolated perfused guinea pig heart preparation and correlated with the accumulation of calcium in the myocardium. Although the SR Ca2(+)-ATPase activity was not affected by ischemia of 40 min, reperfusion of the ischemic myocardium resulted in a definite time-dependent decrease in the enzyme activity. The reduction of SR Ca2(+)-ATPase activity was associated with a concomitant decrease in the enzyme concentration in the isolated SR and was in a good correlation with a substantial accumulation within the myocardium. As the results indicated the possibility that proteolytic degradation by a calcium-activated protease(s) was responsible for the reduction of enzyme activity, we examined for the possible involvement of calcium-activated neutral protease (CANP). However, SR Ca2(+)-ATPase obtained either from the normal hearts or from the hearts after 40-min ischemia was found to be quite resistant to proteolytic actions of the two forms of CANP, i.e., microCANP and mCANP partially purified from the guinea pig heart. These results suggest that a destructive process leading to the degradation of SR Ca2(+)-ATPase is activated by reperfusion, but not by ischemia per se, and that CANP is not implicated in the degradation of SR Ca2(+)-ATPase.
Basic Res Cardiol
PMID:Degradation of sarcoplasmic reticulum calcium-pumping ATPase in ischemic-reperfused myocardium: role of calcium-activated neutral protease. 214 70

Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiovascular system, by removing various regions of the neural crest from early embryos. The neural crest provides both neural (sympathetic and parasympathetic) and ectomesenchymal components to the heart, and selective removal of various areas results in embryos with sympathetically aneural hearts, or persistent truncus arteriosus with or without parasympathetic denervation. Myosin isoform expression was studied in each of these types of hearts using an array of myosin antibodies specific for atrium, ventricle or the conduction system. Myosin expression in experimental hearts was found to follow the normal pattern of development using these antibodies. Actin expression was studied using cDNA probes for the 3' untranslated region of actin mRNA of the alpha-skeletal, alpha-cardiac and beta-actin isoforms. Using slot-blot hybridization analysis, the pattern of actin expression in atrium and ventricle was followed throughout the period of incubation in normal hearts. The pattern of actin expression was found to be abnormal in hearts which were sympathetically aneural and those which had persistent truncus arteriosus combined with parasympathetic denervation. ATPase activity was increased only in atria of hearts with persistent truncus arteriosus. It appears from these experiments that actin isoform expression is influenced in the chick heart by autonomic innervation.
J Mol Cell Cardiol 1990 Sep
PMID:Actin and myosin isoforms in aneural and malformed chick hearts. 214 50

Alterations of cardiac contractility caused by thiamine deficiency were studied on three groups of 2 month old male Wistar rats: B1, fed a thiamine deficient diet, PF pair fed, which received an amount of thiamine free diet determined on the daily consumption of B1 animals, supplemented with appropriate thiamine supply, C ad libitum fed controls. The animals were studied after 35 days of dietary treatment. Force-velocity curves were determined in right ventricle papillary muscles. Shortening velocity was significantly lower in B1 and PF than in C muscles and in B1 than in PF muscles. The ability to develop tension was not altered. Myosin ATPase activity was assayed in preparations of myofibrils and in preparations of purified myosin. Both Ca-Mg activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were significantly reduced in B1 and PF compared to C myocardium. Furthermore Ca-activated ATPase activity was lower in B1 than in PF myocardium. Myosin isoenzyme distribution was determined by pyrophosphate gel electrophoresis of purified myosin preparations. When compared to C animals both B1 and PF animals showed a myosin electrophoretic pattern shifted towards the slow isoform V3; such a shift was more pronounced in B1 animals. Information concerning excitation-contraction coupling was obtained by determining the steady state and transient force-interval relation and by recording transmembrane action potential. B1 and PF myocardium exhibited, when compared to C, a less sensitivity to a reduction of the interval of stimulation, a faster mechanical restitution, a prolonged action potential duration. Such alterations were generally more pronounced in B1 than in PF myocardium. The results support the view that in the rat cardiac contractility is deeply affected by thiamine deficiency. The alterations of cardiac contractility seem to be caused by adaptive mechanisms rather than by cardiac failure and seem to be attributable for a big part to the reduction of food supply.
J Mol Cell Cardiol 1990 Oct
PMID:Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation. 215 36

Na,K-ATPase (or the Na,K-pump) is essential for excitability and contractility of muscle tissue. Previous studies have shown a decrease in the concentration of this pump in endomyocardial biopsies from patients with dilated cardiomyopathy. The effect of congestive heart failure on the concentration of Na,K-ATPase in skeletal muscle was assessed in 16 patients by measurement of binding of 3H-ouabain to biopsies of the vastus lateralis muscle. Ten patients had impaired left ventricular function with an ejection fraction of 0.32 +/- 0.03 and a concentration of the Na,K-pump of 229 +/- 15 pmol/g wet weight in the skeletal muscle, whereas 6 patients had an ejection fraction of 0.66 +/- 0.05 (P less than 0.001) and a concentration of 307 +/- 17 pmol/g wet weight (P less than 0.01). In endomyocardial biopsies, the concentration of Na,K-ATPase was 340 +/- 37 and 500 +/- 39 pmol/g wet weight (P less than 0.025) in patients with impaired and normal ventricular function, respectively. There was a significant correlation between the concentration of the Na,K-pump in the biopsies of the skeletal muscle and ejection fraction, as well as between its concentration in the endomyocardial and skeletal muscular biopsies (r = 0.56, P less than 0.025 and r = 0.72, P less than 0.005, respectively). The decrease in concentration of the pump in skeletal muscle may contribute to the limitation of exercise capacity in congestive heart failure.
Int J Cardiol 1990 Feb
PMID:The concentration of the Na,K-pump in skeletal and heart muscle in congestive heart failure. 215 12

Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.
Basic Res Cardiol
PMID:Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals. 215 97

In this study, the lymphocytes and erythrocytes from peripheral venous blood were used as the study model from which were measured the cellular contents of potassium, sodium, calcium and magnesium in 50 patients with chronic congestive heart failure and 39 control patients. Levels of endogenous digoxin-like substance in the plasma and activities of Na/K ATPase in red cell membrane wer monitored simultaneously. In the patients with heart failure, the intracellular contents of potassium and magnesium were decreased while those of sodium and calcium were increased significantly. The levels of endogenous digoxin-like substance were much higher in the plasma than those either in healthy controls or in patients with heart disease but without congestive failure (273.7 +/- 35.5 vs 23.3 +/- 2.2 and vs 32.9 +/- 3.6 pg/ml, respectively, P less than 0.001 for both). The activities of Na/K-ATPase were much lower in the patients with heart failure than in the controls. Values for intracellular electrolytes were significantly correlated with the rising levels of digoxin-like substance in the plasma. Non-digitalis inotropic therapy was associated with the recovery of these alterations of heart function, with the levels of the digoxin-like substance decreasing and activity of Na/K-ATPase going up. We conclude that endogenous digoxin-like substance might play a role in the imbalance of intra-cellular electrolytes seen in patients with congestive heart failure. Digoxin may exacerbate the loss of intracellular potassium.
Int J Cardiol 1990 Apr
PMID:Intra-cellular electrolyte changes and levels of endogenous digoxin-like substance within the plasma in patients with congestive heart failure. 215 46

Thyroid hormones (TH) have previously been shown to alter the force and velocity of cardiac muscle contractions. To investigate the mechanism responsible for these alterations, excess amounts of thyroxine (T4, 1 microM) were applied on rat heart cells grown in cell culture. We found the following biochemical alterations: a) 40% decrease in the myoglobin content within 2 days; b) 25% increase in the rate of Ca-uptake into sacroplasmic reticulum (SR) in myocytes following chemical skinning; and c) a two-fold increase in Na-K-ATPase activity measured by 86Rb-uptake. These changes support our hypothesis that TH induce the transition of slow-twitch ("red") muscles towards the fast-twitch ("white") muscle type. This may explain the changes in contractile activity known to occur under TH influence.
Basic Res Cardiol
PMID:Thyroxine induces transition of red towards white muscle in cultured heart cells. 216 97

Isolated myocytes of rat heart, and sealed sarcolemmal vesicles of bovine heart, were used to examine the selectivity of the effects of partially reduced oxygen species (generated by a mixture of xanthine and xanthine oxidase) on cardiac sodium pump and several other ion transporters of the plasma membrane. When myocytes were exposed to xanthine plus xanthine oxidase, there were time-dependent inhibitions of ouabain-sensitive 86Rb+ uptake and (Na+ + K+)-ATPase activity that could be prevented by allopurinol, or by catalase and superoxide dismutase; suggesting the involvements of H2O2 or oxygen free radicals in the inhibition of the pump. This inhibition preceded any significant decrease in cellular ATP or in the number of viable cells. While ouabain increased 45Ca2+ uptake by myocytes as expected, exposure to xanthine plus xanthine oxidase decreased 45Ca2+ uptake; suggesting that the Na+, Ca2(+)-exchanger of the intact myocytes is also inhibited by oxygen metabolites. Simultaneous inhibitions of the pump, the Na+, Ca2(+)-exchange, the Na+, H(+)-exchange, and the Na+, Pi-cotransport activities also occurred in sarcolemmal vesicles that were treated with xanthine plus xanthine oxidase. These findings indicate that inactivations of the sodium pump and other sarcolemmal ion carriers are early events in the oxidant-induced damage to the cardiomyocyte. In the rat heart myocytes, a fraction of (Na+ + K+)-ATPase that seems to be more sensitive to ouabain, was inactivated more rapidly upon exposure of myocytes to xanthine plus xanthine oxidase; raising the possibility of the existence of different pump populations with different sensitivities to extracellularly generated oxygen metabolites.
J Mol Cell Cardiol 1990 Aug
PMID:Studies on the specificity of the effects of oxygen metabolites on cardiac sodium pump. 217 59

Ischemia-reperfusion heart cell injury may be mediated, at least in part, through the generation of oxy radicals. Therefore, mechanisms of action of two oxidants on a membrane model, partially purified Na,K,ATPase, were investigated. Effects of H2O2, an oxygen intermediate postulated to play a primary role in reperfusion injury, on the function of the enzyme were time-dependent and potentiated by Fe ions. The inhibition of enzyme activity was prevented by chelators, but not by hydroxyl radical scavengers. The results support the view that the possible mode of enzyme modification involves H2O2-derived, Fe ion-catalyzed, localized ("site-specific") hydroxyl radical formation. The action of hypochlorous acid (HOCl), a powerful oxidant postulated to be produced by activated neutrophils, was quantitatively similar to that of H2O2 plus Fe ions in causing enzyme dysfunction. This is partly because relatively large doses of oxidants were required, due to the presence of physiological anti-oxidant defense mechanisms in the membrane. Although a combination of deferoxamine (Fe ion chelator) and dithiothreitol (DTT) (sulfhydryl reducing agent) was most effective in preventing the enzyme modification, once enzyme inactivation by oxidants is in progress, deferoxamine plus DTT could only arrest further deterioration of the enzyme function. Therefore, the oxidant-induced change in membrane dysfunction advances with time; the advance can be stalled, but the enzyme activity cannot be restored to normal.
Basic Res Cardiol
PMID:Effect of oxidants on Na,K,ATPase and its reversal. 217 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>