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

---

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

Abnormal sodium balance is known to be associated with pre-eclampsia, but no investigations have been conducted concerning the enzyme which regulates active sodium transport at the cellular level. In this study, the enzyme responsible for active sodium transport--Na/K-ATPase and a nonspecific ATPase Mg-ATPase--were assayed in the placenta and in maternal and fetal (cord) erythrocytes of pregnant women with and without pre-eclampsia. Placental ATPase activity was unaffected by pre-eclampsia. However, in infants of pre-eclamptic mothers, fetal erythrocytes were found to have significantly less activity (42 per cent) of both enzymes than fetal erythrocytes from infants of normal mothers. In pre-eclamptic mothers, erythrocyte Mg-atpase activity was significantly less (41 per cent) than normal and Na/K-ATPase activity was slightly decreased (16 per cent). These results indicate that disruption of active sodium transport in fetal erythrocytes is associated with pre-eclampsia and are not inconsistent with the hypothesis of a circulating "toxin."
...
PMID:Na/K- and Mg-ATPase activity in the placenta and in maternal and cord erythrocytes of pre-eclamptic patients. 13 74

Preeclampsia is characterized by enhanced pressor responsiveness to angiotensin II. This report summarizes studies by our laboratory to investigate possible roles for calcium, sodium, membrane pumps, and the vasoactive hormones, atrial natriuretic peptide (hANP) and endothelin, in modulating the change in vascular reactivity characteristic of preeclampsia. Urinary calcium excretion, 1 alpha-25(OH)2D3 levels, and serum free calcium levels were all decreased, whereas parathyroid hormone levels and intraplatelet calcium concentrations were increased in women with preeclampsia. Erythrocyte sodium content was elevated, while red blood cell membrane Na-K-ATPase activity was decreased in patients with severe disease. Preeclamptics also had elevated levels of hANP, which failed to increase further when saline was infused or when blood pressure was increased transiently with angiotensin II administration. Finally, endothelin levels that are reduced in normal gestation, were increased in preeclampsia. While the cause of increased vascular reactivity is still unclear, there appear to be changes in the intracellular cation environment, combined with loss of compensating mechanisms, both at the membrane and humoral level, as well as enhanced concentrations of a potent vasoconstrictor in blood; all which lead to increases in vasoreactivity and blood pressure in preeclampsia.
...
PMID:Vascular reactivity in normal and abnormal gestation. 182 48

1. A ouabain-displacing factor (ODF) was measured in the urine of non-pregnant, normotensive pregnant and hypertensive pregnant women by a receptor-binding assay with sodium, potassium-dependent adenosine triphosphatase. 2. Urinary ODF was significantly increased in normal pregnancy. 3. Greater increases were seen in pregnancy-induced hypertension and pre-eclampsia.
...
PMID:A ouabain-displacing factor in normal pregnancy, pregnancy-induced hypertension and pre-eclampsia. 283 Oct 7

There is increasing evidence for endogenous, circulating compounds that interact with the digitalis receptor of [Na,K]ATPase and with antidigoxin antisera. Circulating levels of these digitalis-like compounds increase in response to fluid or salt loading and appear to play a role in diseases characterized by fluid and salt retention, e.g. renal failure, liver disease, acromegaly, experimental and human hypertension, and preeclampsia. Because of assay nonspecificity, many diverse substances are being measured. Of the few compounds currently identified as having "digitalis-like" activity, none appears to be the natural ligand of the digitalis receptor and none appears linked with hypertension. Nevertheless, research still suggests that digitalis-like factors may have a central role in essential hypertension and related disorders.
...
PMID:Endogenous digitalis-like natriuretic factors. 303 37

An endogenous sodium pump inhibitor, or digitalis-like factor (DLF), has been postulated to mediate essential hypertension. It may also play a role in preeclampsia. However, studies of this factor in hypertensive pregnancy have not provided consistent findings. Part of this may be due to the absence of subclassification of pregnant women with pregnancy-induced hypertension (PIH) when assessing these parameters. In this study we explored serum DLF and digoxin-like immunoreactive factor (DLIF) in insulin-dependent diabetic (IDDM) women with normotensive pregnancies or PIH, comparing them to each other and to nondiabetic pregnant women. Our results demonstrated that nondiabetic women with preeclampsia (PE, PIH with proteinuria) had significantly increased serum DLF and DLIF compared to normotensive pregnant women (NL BP). Women with transient hypertension of pregnancy (THP, PIH without proteinuria) had intermediate values (DLF. NL BP: 3.3 +/- 0.6, THP: 4.8 +/- 1.1, PE: 7.6 +/- 1.3% inhibition [Na,K]-ATPase, P < .05 ANOVA; DLIF. NL BP: 0.22 +/- 0.02, THP: 0.28 +/- 0.03, PE: 0.35 +/- 0.02 ng digoxin equivalents/mL, P < .05 ANOVA). Pregnant normotensive IDDM women had significantly higher serum DLF and DLIF activity than their nondiabetic counterparts (DLF. non-IDDM NL BP: 3.3 +/- 0.6 v IDDM NL BP: 8.8 +/- 1.2% inhibition [Na,K]-ATPase, P = .0008; DLIF. non-IDDM NL BP: 0.22 +/- 0.02 v IDDM NL BP: 0.31 +/- 0.02 ng digoxin equivalents/mL, P = .005).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Digitalis-like factor and digoxin-like immunoreactive factor in diabetic women with preeclampsia, transient hypertension of pregnancy, and normotensive pregnancy. 873 86

Metabolic indicators of glucose and lipid metabolism, i.e. glucose turnover, insulin concentration in plasma, insulin clearance, concentrations of non-esterified fatty acids (NEFA), glycerol and potassium were investigated in nine ewes during three reproductive states in order to examine their importance for development of subclinical ketosis. The increase of insulin in plasma was measured after a continuous 60 min intravenous infusion of glucose (4.9 mmol.min-1). Turnover of glucose and insulin clearance were quantified during a combined euglycemic, hyperinsulinemic clamp. Insulin was consecutively infused in doses of 5 and 10 mU.kg-1.min-1 for about 2 1/2 hours, each. Plasma glucose concentration was adjusted to 5.3 to 5.8 mmol.l-1. The experiments were carried out during non-pregnancy and non-lactation, 4 weeks to 3 days before lambing and 3 to 4 weeks after lambing, each during normo- and hypocalcemia. Hypocalcemia (0.9 to 1.0 mmol Ca2+.l-1) was induced by continuous i.v. infusion of a 5% Na-EDTA solution. Infusion rate was continuously adjusted. The glucose induced increase in plasma insulin concentration was significantly lower during late pregnancy compared to peak lactation and non-pregnancy (46.3, 62.4 and 128 mU.l-1, respectively). The insulin clearance during a hyperinsulinemic clamp with 5 mU.kg-1.min-1 was significantly less during late pregnancy compared to peak lactation and non-pregnancy (3.7, 6.0, 4.8 ml.kg-1.min-1, respectively). The concentrations of NEFA and glycerol in plasma during the infusion of 5 mU insulin.kg-1.min-1 were significantly higher during late pregnancy than during non-pregnancy (NEFA: 0.41, 0.04 mmol.l-1; glycerol: 96, 29 mumol.l-1, respectively). The results showed that insulin responsiveness was significantly reduced in sheep during late pregnancy. The insulin-mediated uptake of glucose by muscle and fat tissues and the insulin-mediated inhibition of lipolysis were significantly reduced during late pregnancy compared to non-pregnancy and lactation. The diminished responsiveness of target tissue towards insulin during late pregnancy predisposed the animals for development of subclinical ketosis. Hypocalcemia exaggerated this situation by its inhibitory effect on hepatic gluconeogenesis and by enhancing insulin resistance of target tissues. The factors which are responsible for the altered responsiveness of target tissues towards insulin during late pregnancy are yet unknown. The potassium concentration in plasma showed a proportional increase with increase of the energy deficit of the target tissues. This effect could have been exerted by a decrease in cellular concentration of ATP and a concomitant reduction of the activity of Na(+)-K(+)-ATPase. The indicators of glucose and lipid metabolism which were examined in this study showed marked individual variation, particularly during late pregnancy. The marked changes of these indicators with reproductive stages as well as their great variation between individual sheep support the assumption that they are of significance for the development of pregnancy toxemia in sheep.
...
PMID:[Effect of insulin on glucose and and fat metabolism in ewes during various reproductive states in normal and hypocalcemia]. 941 Jul 23

We determined Na,K-ATPase activity and cholesterol/phospholipid ratio of maternal and cord red blood cell ghosts from either normotensive or preeclamptic pregnant women. The Na,K-ATPase activity of the red cell ghosts from neonatal blood is significantly lower (25-32%) as compared with the ATPase activity of the maternal red cell ghosts, regardless of the presence or not of preeclampsia. This diminution in Na,K-ATPase activity of the neonatal red blood cell ghosts could be due to an increase in the cholesterol/phospholipid molar ratio of the membrane. The Na,K-ATPase activity of the red blood cell ghosts from pregnant women was unaffected by preeclampsia; however, fetal red blood cell ghosts from infants of preeclamptic mothers showed a significantly lower ATPase activity (20%) than fetal red blood cell ghosts from infants of normotensive mothers. A low Na,K-ATPase activity in the neonatal red blood cells from mothers with preeclampsia could be an indication of an important modification of the physiological role of this enzyme.
...
PMID:Preeclampsia and Na,K-ATPase activity of red blood cell ghosts from neonatal and maternal blood. 1115 Aug 23

Elevated Na(+)/H(+) exchanger activity and intracellular acidosis have previously been demonstrated in white blood cells isolated from women who have suffered from a pre-eclamptic pregnancy. The mechanisms underlying this abnormality and the implications in pre-eclamptic pregnancies are, at present, unclear. In this study, we used neutrophils from third trimester pre-eclamptic patients and third trimester normotensive pregnant controls to determine Na(+)/H(+) exchanger isoform-1 (NHE-1) activity and intracellular pH. This was performed using a well-validated technique involving flurometry and a pH sensitive dye, 2,7'Bis-(carboxyethyl) 5.6 carboxyfluorescein acetomethyl ester (BCECF-AM). Time course experiments were performed to assess the contribution of plasma factors to intracellular pH measurements. Plasma digoxin-like factor (DLF) was assessed in both patients and normotensive controls. Neutrophil intracellular pH was significantly lower in the pre-eclamptic patients (7.15 +/- 0.050) compared with the normotensive pregnant controls (7.36 +/- 0.027; P<.001). NHE-1 activity (in mmol/L/min) was significantly higher in the pre-eclamptics (32.4 +/- 1.9) compared with the normotensive neutrophils (27.1 +/- 1.6; P =.038). Times course experiments showed that mean pre-eclamptic intracellular pH increased from 7.11 +/- 0.049 to 7.25 +/- 0.043 after 2 hours of incubation. DLF, measured as amount of inorganic phosphate liberated from adenosine triphosphate (ATP), was significantly lower when plasma from the pre-eclamptic patients was incubated with the enzyme compared with plasma from the normotensive pregnant women (54.9 +/- 2.6 nmol/mL plasma v 63.91 +/- 1.7 nmol/mL plasma, n = 6, P =.018 unpaired Student's t test). The results suggest that elevated NHE-1 activity and intracellular acidosis are intermediate phenotypes in women who have pre-eclampsia. Intracellular pH may have been affected by plasma as shown in the time course experiments. DLF, an inhibitor of Na(+)/K(+)ATPase, may contribute to this intracellular acidosis in pre-eclamptic neutrophils.
...
PMID:Neutrophil intracellular pH and Na+/H+ exchanger activity in pre-eclampsia. 1252 67

Digoxin-specific Fab (Digibind) is a mixture of antidigoxin Fab fragments prepared from sheep sera and is used as a treatment for digoxin poisoning. Digoxin-specific Fab has been shown to neutralize an endogenous Na+/K+ ATPase inhibitor (endogenous digoxin-like Na+/K+ ATPase regulatory factor; EDLF) in rats and humans and to lower blood pressure. Although the exact structure of EDLF is unknown, compounds identical to or structurally related to ouabain, bufalin, and marinobufagenin have been detected in mammalian plasma. In this study, some structural characteristics of EDLF were inferred from the ability of digoxin-specific Fab to neutralize the Na+/K+ ATPase inhibitory activity of several known cardenolides and bufodienolides. Additional structural information was obtained from [3H]ouabain binding and enzyme-linked immunosorbent assay experiments. Digoxin-specific Fab had the ability to interact to some extent with all of the cardenolides and bufodienolides tested. However, digoxin-specific Fab was more than 20-fold more potent in neutralizing ouabain and bufalin than marinobufagenin. The antihypertensive effect of digoxin-specific Fab seen in preeclampsia and animal models of hypertension may therefore be due to a molecule identical to or structurally similar to ouabain or bufalin.
...
PMID:Characterization of the neutralizing activity of digoxin-specific Fab toward ouabain-like steroids. 1498 68

We previously reported that in preeclampsia Ca-ATPase activity diminishes about 50% in red blood cells, myometrium and syncitiotrophoblast plasma membranes. In this work, we measured the active Ca++ uptake by inside-out vesicles of human red blood cells from preeclamptic and normotensive pregnant women. Active calcium uptake by the vesicles was diminished by 49+/-3% in the preeclamptic women as compared to the gestational controls ( 8.06 +/- 0.11 nmol Ca++/mg protein min, gestational controls; 4.08 +/- 0.1 nmol Ca++/mg protein min, preeclamptics). This lowered calcium uptake correlates well with the lowered Ca-ATPase activity found in the red blood cells ghosts of the preeclamptic women (17.05 +/- 0.96 nmol Pi/mg protein min, gestational controls; 8.85 +/- 0.45 nmol Pi/mg protein min, preeclamptics). The reduced calcium uptake and Ca-ATPase activity of the red cell membranes both appear to be associated with a high level of lipid peroxidation. Thus there is a diminution in the active transport of calcium in the red blood cells of preeclamptic women. If this also occurs in other cell types of the preclamptic women, it could result in an increase in their cytosolic calcium concentration which might be responsible, in part, for some of the symptoms of this disease.
...
PMID:Lipid peroxidation and active calcium transport in inside-out vesicles of red blood cells from preeclamptic women. 1500 33


1 2 3 4 Next >>

---