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)

Erythrocyte (Ca2+ + Mg2+)-ATPase activity and calcium content were determined in 15 uremic-hemodialyzed patients and 15 normal controls. A decrease in the activity of the enzyme (mean +/- SD = 65 +/- 7 vs. 79 +/- 12 mumol Pi/g Hb/h, p less than 0.001) and a parallel increase in the calcium content (17.2 +/- 6.4 vs. 5.1 +/- 4.2 mumol/L RBC, p less than 0.05) were found in the patients' erythrocytes when compared with those of the controls. It is proposed that malfunction of the calcium pump in hemodialyzed uremic patients is pathophysiologically significant in the accumulation of intracellular calcium. The increased intracellular calcium found in other tissues in uremia may be the result of the systemic malfunction of (Ca2+ + Mg2+)-ATPase in this disorder.
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PMID:Decreased erythrocyte (Ca2+ + Mg2+)-ATPase activity in hemodialyzed uremic patients. 183 88

Deproteinized plasma from patients with renal failure had an inhibitory effect on Na,K ATPase activity measured in vitro by a linked-enzyme assay. No inhibitory effect was observed with plasma from normal subjects or from patients undergoing chronic ambulatory peritoneal dialysis. The inhibition of Na,K ATPase whether measured by the linked-enzyme assay or by 86Rb uptake in guinea pig aortic strips was decreased acutely by a single hemodialysis treatment, but was unaffected during a time-control study or ultrafiltration. Changes in Na,K ATPase activity and in Rb uptake were correlated, indicating that the presence of the enzyme inhibitor in uremic plasma was associated with depressed Na pump activity. Change in inhibition of Na,K ATPase activity did not correlate with change in body weight. Dialysis in vitro against a membrane of molecular weight 3,500 cut-off decreased the inhibitory effect of uremic plasma on Na,K ATPase. It was concluded that a dialyzable, low-molecular-weight Na,K ATPase inhibitor circulates in uremia but has no demonstrable role in volume homeostasis.
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PMID:Effect of dialysis on circulating Na,K ATPase inhibitor in uremic patients. 215 80

The changes of RBC Ca2(+)-ATPase activity and red cell calcium concentration during dialysis were observed in 19 patients with uremia. The results showed that in 12 patients treated by haemodialysis the RBC Ca2(+)-ATPase activity was lowered an average of 35 U than that in the controls (P less than 0.001); whereas red cell calcium was increased about 5 times (P less than 0.001). After a four-hour haemodialysis, the Ca2(+)-ATPase activity increased 20 U (P less than 0.05); and red cell calcium decreased 45 mumol/L cells (P less than 0.05). In 7 patients treated by CAPD the RBC Ca2(+)-ATPase activity was reduced to 60% of that in the controls (P less than 0.001); and red cell calcium was about 5 times as high as that in the controls (P less than 0.001). After one month of CAPD, the Ca2(+)-ATPase activity increased only 10 U (P greater than 0.05); but red cell calcium decreased 66 mumol/L cells (P less than 0.01).
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PMID:[Changes in RBC Ca2(+)-ATPase activity and red-cell calcium concentration during dialysis in patients with uremia]. 215 34

Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and "calmodulin"-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of normal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysis also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean +/- SEM 21.2 +/- 2.8 mumol/L of cells; n = 28) was higher than in controls (4.9 +/- 0.3 mumol/L of cells; n = 24; p less than 0.001). Hemodialysis had no effect on cell calcium level. Both basal and "calmodulin"-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p less than 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 +/- 217.0 mumol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 +/- 206.8 mumol/L of cells per 0.5 hours after hemodialysis (p less than 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 +/- 1.15 mumol/L of cells per hour versus 4.61 +/- 0.39 mumol/L of cells per hour (p less than 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p less than 0.01). These results indicate that RBC calcium level is elevated in patients with ESRD and suggest that a dialyzable uremic factor inhibits RBC CaATPase activity and thereby calcium efflux, which may account for the elevated cell calcium level. The increased calcium influx further increases cellular calcium level. These abnormalities are associated with spherocytosis and echynocytosis and may contribute to the shortened survival of RBCs in uremia.
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PMID:Red blood cell calcium homeostasis in patients with end-stage renal disease. 252 34

The universal presence of a binding site for cardiac glycosides on Na+-K+-ATPase has engendered speculation as to whether it also serves as a receptor for an endogenous digitalis-like hormone or autacoid. If such a hormone were to exist, it could play a role in sodium homeostasis and in the pathophysiology of primary hypertension and uremia. However, we believe that this hypothesis rests on unproven assumptions. Although typical of many toxins and drugs, binding to a single protein that acts as both its receptor and effector mechanism at the cell membrane, thereby directly affecting transmembrane ion flux, would be unusual for a hormone or autacoid. As an alternative hypothesis for the evolutionary conservation of the cardiac glycoside binding site, we suggest that its endogenous ligand may exist within the cell. After cotranslational insertion of the alpha- and beta-subunits into the membrane of the rough endoplasmic reticulum, Na+-K+-ATPase, like most integral membrane proteins, 1) must be targeted through a complex network of intracellular organelles to the correct plasmalemmal domain, 2) must be monitored for appropriate protein conformation and subunit assembly, and perhaps 3) could have its catalytic function regulated before insertion in the cell membrane. Because the lumina of the endoplasmic reticulum, Golgi, and other organelles and vesicles are topologically equivalent to the outside of the cell, all three functions could be subserved by an intraorganellar ligand for the cardiac glycoside binding site.
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PMID:The search for the endogenous digitalis: an alternative hypothesis. 254 19

Loss of lean body mass occurs frequently in patients with acute or chronic renal failure, but the mechanism(s) causing this abnormality are unknown. Using animal models of experimental uremia, it was found that excess lactate formation in muscle is directly related to the rate of protein breakdown. This suggests that abnormal energy metabolism may be one mechanism for protein wasting. A second mechanism involves metabolic acidosis. Metabolic acidosis activates the catabolism of protein and amino acids in muscle of uremic rats independently of azotemia. Defects in sodium transport by Na,K-ATPase and the Na/K/Cl cotransport system suggest that intracellular ions including hydrogen may be abnormal. If this were the case, uremia would increase the susceptibility to the catabolic effect of metabolic acidosis.
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PMID:Protein and amino acid metabolism in uremia: influence of metabolic acidosis. 263 59

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.
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PMID:Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats. 283 46

The satisfactory analysis of the Na/K ATPase, its pumping component and the mechanism of action of the inhibitor digitalis remains elusive; yet the controversial inotropic effect of digitalis in the clinical setting has been known for over a century. There are also conflicting reports of the effect of urea and uremia on the cardiovascular system, and the evidence as it exists, suggests that urea may have two effects on the intact heart, by virtue of its extent of action on hydrogen bonding of water molecules, determined by which type of muscle constitutes the myocardium. If different types of myocardium do exist, they could well respond differently to inotropic agents. Evidence suggests that two types of myocardia, relatively stress resistant or susceptible may exist, analagous to known skeletal muscle differences.
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PMID:Are there stress resistant and susceptible myocardia? 285 Apr 51

In hypothyroid rats (TX), the isotonic fluid reabsorption (Jv), that is closely linked to the transepithelial sodium transport (JNa), is impaired. The administration of physiological doses (10 micrograms/kg body weight per day) of tri-iodothyronine (T3) doubles Jv in three days (TX+T3). This phenomenon could be explained by several mechanisms: a direct stimulation of Na-K-ATPase, an increase in the Na+ entry step, changes in the permeability properties of the luminal and/or basal lateral membranes. Using a kinetic microassay, Na-K-ATPase activity was measured in early (S1) and late (S2) proximal tubules segments isolated from control, TX, and TX+3T3 animals. In TX rats the enzyme activity was lower (70%) in both segments versus control rats, it remained unchanged after 3 days, and it increased after 7 days of T3 substitution. The Na+ permeability of brush border membrane (BBM) vesicles isolated from TX and TX+T3 rats was identical. However the valuation of the K+ membrane permeability by in vivo perfusion of the lumen and peritubular space of proximal tubules of TX rats, with perfusate containing the K+ ionophore valinomycin (1 microgram/ml), induced a significant increase in Jv that accounted for 40% of that elicited by T3. Taken together, the in vivo and in vitro experiments suggest that the early effect on Jv of physiological doses of T3 cannot be explained by a direct action of T3 either on the Na+ entry step across the BBM or on the Na+ exit step (i.e., the Na-K-ATPase), but rather by an increase in K+ permeability of proximal tubular cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Uremia Invest
PMID:The use of micropuncture, isolated tubule, and vesicle technique in the study of the action of thyroid hormones on the proximal tubule function. 302 Jul 58

The causes of central nervous system (CNS) dysfunction in uremia are not well known and are not completely reversed by dialysis. This problem was investigated in synaptosomes, which are membrane vesicles from synaptic junctions in the brain. We measured Na uptake under conditions of control, veratridine stimulation, and tetrodotoxin inhibition, in synaptosomes from normal and acutely uremic (blood urea nitrogen, 250 mg/dl) rats. In the control state, maximal Na uptake was 2.2 +/- 0.2 and 1.9 +/- 0.3 nmol/mg of protein in normal and uremic synaptosomes, respectively. With veratridine stimulation, Na uptake was increased by 1.9 and 3.6 nmol/mg of protein in normal vs. uremic rats (P less than 0.001). The increased veratridine-stimulated Na uptake observed in uremia could be due either to increased membrane permeability to Na or decrease in the Na-K ATPase pump activity. To investigate this, we studied the Na-K ATPase pump function by evaluating uptake of K (using rubidium as a tracer), uptake of Na during ATP stimulation, and inhibition of Rb and Na uptake by ouabain. In uremic rats both Rb uptake and ATP-stimulated Na uptake were significantly less than in normals (P less than 0.005). This suggests a defect in the Na-K ATPase pump. Membrane permeability for Na was then evaluated both by measuring initial Na uptake, and with addition of valinomycin. No change in Na uptake pattern was observed with valinomycin, and initial Na uptake was not significantly different in normal versus uremic synaptosomes. These data show that (a) in uremic rats veratridine-stimulated Na accumulation is significantly greater than normal; (b) the increased Na accumulation observed in uremia appears to be due to alterations in Na-K ATPase pump activity; and (c) the altered Na accumulation observed is probably not due to a uremic environment, but may be secondary to a physiologic alteration in synaptosomal function due to the uremic state. These abnormalities may affect neurotransmission and may be associated with the CNS alterations observed in uremia.
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PMID:Abnormal sodium transport in synaptosomes from brain of uremic rats. 400 50


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