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)

In myocardial hypertrophy and heart failure a series of adaptational changes occur some multiplying contractile units, others slowing shortening velocity and increasing economy of contraction. The demonstration of energy-saving mechanisms in heart failure has prompted further investigations of energy providing and utilizing metabolic pathways. The use of myocardial ATP as a substrate occurs mainly at the myosin-ATPase and at the Ca-ATPase of the sarcoplasmic reticulum. As the Michaelis constant of both enzymes for ATP is in the micromolar (microM) range, whereas cellular ATP content is about 5000 microM, these enzymes are not controlled by the availability of ATP as a substrate. In experimental heart failure in large animals, normal or reduced creatine phosphate levels (in most cases together with normal adenine nucleotides) have been described. Reduced creatine phosphate is found in models with increased oxygen consumption, and creatine phosphate may buffer the ATP pool in these models. In human heart failure due to dilated cardiomyopathy, where resting oxygen consumption per unit mass and lactate extraction are normal in most patients, normal adenine nucleotides, creatine phosphate, and mitochondrial function have been described in the initial studies. These results have been challenged by one study showing decreased ATP levels in dilated cardiomyopathy, correlating with the decrease in ejection fraction. However, only ATP has been measured in this study, whereas total adenine nucleotides may be a more suitable parameter. Recently published results have again demonstrated normal ATP and total adenine nucleotides in human heart failure. In the same patients, significantly decreased myocardial norepinephrine was measured, indicating that metabolic changes had occurred in these hearts, but were independent of adenine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
Basic Res Cardiol 1992
PMID:Adenine nucleotide metabolism and contractile dysfunction in heart failure--biochemical aspects, animal experiments, and human studies. 149 76

The formation of palmitoylcarnitine is catalyzed by carnitine palmitoyl-transferase (CPT-I) and this catalysis is the first committed step in beta-oxidation. The malonyl-CoA-inhibited isoform appears to be distinct from latent (CPT-II) activity, which is localized to the matrix side of the mitochondrial inner membrane. Sarcoplasmic reticulum from canine cardiac muscle was fractionated on a discontinuous sucrose density gradient into three major bands, all of which contained Ca(2+)-ATPase activity. Only the fraction that banded at a concentration of 38% surcrose was slightly contaminated by mitochondria. Peroxisomal uricase was low or absent in fractionated SR. All sarcoplasmic reticulum fractions contained malonyl-CoA-sensitive medium- (COT) and long-chain (CPT) carnitine acyltransferase activities. CPT activity decreased in sarcoplasmic reticulum when Triton X-100 was present. Carnitine acyltransferase activities were inactivated by preincubating the sarcoplasmic reticulum with the sulfhydryl reagent, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In contrast, mitochondrial CPT-II activity was stable in the presence of DTNB and activated by Triton X-100. Western blots of mitochondria and sarcoplasmic reticulum fractions showed that the mitochondrial fractions reacted with antibody to mitochondrial CPT-II but not with SR protein when both were added at comparable specific activities. The data suggest that cardiac SR contains a unique malonyl-CoA-sensitive isoform of CPT, and that synthesis of acylcarnitine may occur in the microenvironment of Ca2+ transport, where the extent of production of acylcarnitine is controlled by cardiac acetyl-CoA carboxylase activity.
J Mol Cell Cardiol 1992 Mar
PMID:Evidence for malonyl-CoA-sensitive carnitine acyl-CoA transferase activity in sarcoplasmic reticulum of canine heart. 162 48

Cardiac hypertrophy resulting from a chronic mechanical overload is the physiological adaptation of the heart to a disease. From a physiological point of view it is characterized by a slowing of the maximum unloaded shortening velocity and an increased duration of the action potential. This slowing allows the heart to maintain a normal maximum tension at a slower rate. In addition, the heart produced per gram of tension is normalized and the efficiency returns to normal. From a biological point of view the expression of two protooncogenes and of two heat-shock proteins genes is enhanced at the beginning of the overload. The biological determinants of the changed shortening velocity are species-specific. An isomyosin shift plays a major role in some species, e.g., rat, while in others, e.g., man, changes in membrane proteins are determinant. The density in Ca2+ channels remains unmodified, with a significant drop in the density of Ca2+ ATPase of SR, adrenergic and muscarinic receptors, and a slowing of the Na+/Ca2+ exchange. More complex changes occur at the level of the Na+, K+ ATPase. One of the principal consequences of these findings is that most of the usual targets of inotropes are modified and that new drugs have to be conceptualized accordingly.
Basic Res Cardiol 1991
PMID:Remodeling of the heart in chronic pressure overload. 164 66

Digoxin like immunoreactive factor (DLIF), has been implicated on the effect of sodium in essential hypertension. The different concentration of DLIF as a function of sodium intake was demonstrated in animal experience by some authors. In this work the urinary DLIF excretion is evaluated by RIA and its biological activity by Na+/K+ ATPase inhibition, in 5 urine samples at the end of a free sodium diet week and in 10 urine samples in the last day of a week with 250 mg sodium diet. The urinary DLIF excretion after the free sodium diet week was 0.3460 +/- 0.055 and at the end of sodium restriction diet week of 0.2910 +/- 0.061 nmol/l. Although the DLIF values in the sodium restriction week were smaller than the DLIF values of the free sodium diet week, there was no statistical difference (p = 0.113). In five patients the DLIF could be evaluated at the end of the first and second weeks without changes in the hypertensive therapeutics, with clonidine and nifedipine, along the two weeks. In these five patients at the end of the free sodium diet week and at end of the sodium restricted diet week were 0.3460 +/- 0.055 and 0.2780 +/- 0.060 nmol/l. The reduction of urinary DLIF excretion in the sodium restricted diet week, was significative (p = 0.020). The results of the Na/K ATPase inhibition in the same five patients were: 34.6 +/- 6.51% at the end of the free sodium diet week and 31.7 +/- 6.32% at the end of the sodium restricted diet week, the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Rev Port Cardiol 1991 Jan
PMID:[Determination of endoxin in hypertensive patients]. 164 7

Prevention of cardiotoxicity without interfering with the therapeutic efficacy of adriamycin is a very crucial question. We have investigated the activity of beta-adrenoceptor coupled to guanine nucleotide binding regulatory proteins (G-proteins) and Ca(2+)-ATPase activity in experimental adriamycin-induced cardiotoxicity and the influence of metoprolol treatment on these variables. Adriamycin was administered to rats intravenously as a single dose of 6 mg/kg, and metoprol was continuously given by means of implanted osmotic pumps. beta-Adrenoceptor characteristics were measured by radioligand-binding experiments and by basal and stimulated adenylyl cyclase activity. Northern blot and dot blot analysis was used to quantify G-protein mRNA. It was shown that adriamycin did not induce any change in the total beta-adrenoceptor density, nor did the high affinity agonist binding to beta-adrenoceptor change. Adriamycin did not induce any alteration in the amount of mRNA encoding for stimulatory (Gs) or inhibitory (Gi) G-proteins. Also, basal and stimulated adenylyl cyclase activities were identical in the different experimental groups. In contrast, the Ca(2+)-ATPase was shown to increase in adriamycin-treated rats compared to control rats (45 +/- 3.8 versus 23 +/- 1.2 mumol Pi/mg/h, P less than .01). Metoprolol was shown to normalize this increase (29 +/- 2.1 mumol Pi/mg/h). Thus, it may be concluded that in experimental adriamycin-induced cardiotoxicity, despite Ca(2+)-overloading, the beta-adrenoceptor-G protein-adenylyl cyclase system remains intact. Metoprolol seems to prevent Ca(2+)-overloading independently of the beta-adrenoceptors studied here.
Basic Res Cardiol
PMID:Effect of metoprolol on activity of beta-adrenoceptor coupled to guanine nucleotide binding regulatory proteins in adriamycin-induced cardiotoxicity. 165 44

Hypertrophy of the cardiac myocytes resulting from a mechanical overload may be responsible for major membraneous modifications, either at a sarcolemmal or at a sarcoplasmic level. In the present report, evaluation of several sarcolemmal markers such as beta-receptors, muscarinic receptors or (Na+,K+)-ATPase has been realized on an experimental model of cardiac hypertrophy performed on adult rats. Special attention has been taken to compare results expressed in densities or expressed in number of receptors present at the cellular level. For example, the beta-receptors density was 30% decreased whereas calculations of number of receptors present in the myocytes revealed an unchanged number (around 20,000 in both groups). The unmodified number could suggest a non regulation for the genes coding for the receptors.
Acta Cardiol 1991
PMID:Membrane proteins of the myocytes in cardiac overload. 165 72

Lysophosphatidylcholine (LPC) accumulates in myocardial tissues during ischemia, and has toxic effects which may contribute to the arrhythmias and relaxation abnormalities that occur during acute ischemia. These effects of LPC may be mediated in part by calcium overload. To test this hypothesis, spontaneously contracting cultured embryonic chick ventricular myocytes were superfused with various concentrations of LPC (10, 50 and 100 microM) while effects on contractile motion (video motion detector) and changes in free intracellular calcium ion concentration ([Ca2+]i indo-1 fluorescence) were determined. At concentrations greater than or equal to 10 microM, a dose-related, time-dependent effect occurred after exposure to LPC, consisting of the development of contracture and marked elevation of [Ca2+]i. LPC also produced a dose-related, time-dependent inhibition of K+ uptake, indicating there was inhibition of the Na(+)-K+ ATPase Na+ pump. However, the LPC-induced increase in [Ca2+]i was not due to Na+ overload caused by inhibition of the Na(+)-K+ ATPase Na+ pump because superfusion with a zero-Na+ solution did not prevent an increase in [Ca2+]i after LPC exposure; and the increase in [Ca2+]i after exposure to LPC occurred too rapidly to be accounted for by Na+ pump inhibition. Removal of extracellular Ca2+ prevented the rise in [Ca2+]i, after exposure to LPC but treatment with verapamil failed to inhibit the increase in [Ca2+]i induced by LPC. We conclude that LPC produces contracture due to an increase [Ca2+]i. These effects are seen at concentrations of 10 microM and greater, are not due to altered Na(+)-K+ ATPase Na+ pump or calcium channel function, and are probably related to the detergent properties of this amphiphile. There effects may account in part for myocardial dysfunction during ischemia in intact tissue.
J Mol Cell Cardiol 1991 Jun
PMID:Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma. 165 42

We have demonstrated for the first time the isolation of sarcoplasmic reticulum (SR) membranes from adult rat ventricular myocytes obtained from a single rat heart. The myocyte SR preparation exhibits similar Ca(2+)-transport and Ca2+/K(+)-ATPase activity as well as a similar protein profile to SR membranes isolated from intact rat heart tissue. This SR preparation exhibited a Ca2+/K(+)-ATPase activity of 371 +/- 55 nmol/min/mg protein (mean +/- S.E.M.; n = 5) and an oxalate-stimulated Ca(2+)-uptake activity of 103 +/- 4 nmol/min/mg protein (mean +/- S.E.M.; n = 6). Pretreatment of the SR vesicles with 5 microM ruthenium red increased the oxalate-stimulated Ca(2+)-uptake to 204 +/- 12 nmol/min/mg protein demonstrating the presence of junctional SR membranes. Sodium dodecyl sulphate polyacrylamide gel electrophoresis shows that the isolated SR membranes contained protein bands at 430 (Ca(2+)-release channel), 100 (Ca2+/K(+)-ATPase), 55 (calsequestrin and/or calreticulin) and 53 kDa (glycoprotein). Western blots of myocyte SR membranes stained with ruthenium red detected 2 major Ca(2+)-binding protein bands in this preparation at 53-55 kDa (calsequestrin and/or calreticulin) and 97-100 kDa (Ca2+/K(+)-ATPase). The presence of phospholamban, a regulatory protein of the Ca2+/K(+)-ATPase of cardiac SR, was confirmed in the myocyte SR membranes by western blots probed with a monoclonal antibody to phospholamban. Isoproterenol stimulation of intact [32P]orthophosphate equilibriated myocytes was associated with an increase in the phosphorylation of 3 distinct proteins (27, 31 and 152 kDa) in myocyte homogenates. The 27 kDa phosphorylated protein was identified in purified SR membranes as phospholamban my migration on electrophoretic gels and by immunoblotting. The ability to prepare SR membranes from intact isolated adult rat ventricular myocytes makes this system a potentially useful model for the study of SR regulation by protein phosphorylation.
J Mol Cell Cardiol 1991 Oct
PMID:Isolation and characterization of purified sarcoplasmic reticulum membranes from isolated adult rat ventricular myocytes. 166 Sep 35

Rats, subsequent to loss of a large amount of left ventricular free wall due to surgically-induced myocardial infarction, form a good model of congestive heart failure. Since depressed cardiac pump function is the hallmark of heart failure, it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Because Ca2+ movements in the sarcolemmal membrane are known to involve Ca(2+)-channels, Na(+)-Ca2+ exchange, Ca(2+)-pump, Na(+)-K+ ATPase, beta-adrenoceptors and alpha-adrenoceptors directly or indirectly, the status of these mechanisms was examined by employing rats at different degrees of congestive heart failure. The left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. The number of Ca2+ channels in the myocardium was depressed in moderate and severe stages of heart failure. Furthermore, depressions in sarcolemmal Na(+)-Ca2+ exchange activity and beta-adrenoceptor number were associated with the development of early stages of heart failure, whereas sarcolemmal Na(+)-K+ ATPase activity was decreased and the number of alpha-adrenoceptors was increased at moderate and severe stages. The Ca(2+)-pump activities were not altered in failing hearts. Thus it appears that changes in Na(+)-Ca2+ exchange as well as beta-adrenoceptors and Ca2+ channels may contribute towards decreasing Ca2+ influx at early and moderate stages of congestive heart failure, respectively. On the other hand, changes in alpha-adrenoceptors and Na(+)-K+ ATPase may act as compensatory mechanisms for maintaining Ca2+ influx at moderate and late stages of congestive heart failure.
Basic Res Cardiol 1991
PMID:Experimental congestive heart failure due to myocardial infarction: sarcolemmal receptors and cation transporters. 166 5

A monoclonal antibody against phospholamban has been reported to increase Ca2+ uptake by cardiac sarcoplasmic reticulum. We compared the effect of this antibody on Ca2+ pump ATPase activity of cardiac sarcoplasmic reticulum vesicles to the effect of cAMP-dependent phosphorylation of phospholamban. The antibody markedly stimulated the Ca(2+)-dependent ATPase activity in parallel to the increase in Ca2+ uptake by cardiac sarcoplasmic reticulum. When the Ca(2+)-dependent profile of the ATPase activity was compared, the KCa was shifted from 1.24 to 0.62 microM by the antibody, whereas cAMP-dependent phosphorylation of phospholamban shifted the KCa to 0.84 microM. When cardiac sarcoplasmic reticulum vesicles were treated with both cAMP-dependent protein kinase and the antibody, the stimulation was the same as that with the antibody alone. Thus, the Ca2+ pump ATPase seems to be fully activated by the antibody. The stoichiometry between Ca2+ uptake and ATPase rate was around 1 and no significant change was observed by the treatment with the antibody. Therefore, the stimulation of Ca2+ uptake of cardiac sarcoplasmic reticulum by the antibody occurred by the stimulation of Ca2+ pump ATPase, not by other mechanisms such as channel activity of phospholamban. These results indicate that the binding of the antibody to phospholamban produces essentially the same mode of action on Ca2+ pump ATPase as that of phospholamban phosphorylation. The antibody and phospholamban phosphorylation appear to release the inhibitory action of phospholamban on Ca2+ pump ATPase, resulting in the stimulation of Ca2+ pump.
J Mol Cell Cardiol 1991 Nov
PMID:Effects of monoclonal antibody against phospholamban on calcium pump ATPase of cardiac sarcoplasmic reticulum. 166 13


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