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)

We have demonstrated that repetitive injections of cadmium into rats leads to the abrupt development of Fanconi syndrome after the renal cortical concentration of cadmium has increased approximately eighty-fold. The syndrome is temporally associated with a fall in both Na-K-ATPase activity and ATP levels, suggesting a possible causal relationship between altered proximal tubular transport and inhibition of the ATP-Na-K-ATPase transport system.
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PMID:Cadmium-induced experimental Fanconi syndrome. 12 88

The administration of 1.5 or 9.0 mmoles/kg ip of maleate to rats induced, in addition to renal alterations similar to those occurring in the Fanconi syndrome, a decline in the intestinal mucosa (Na+-K+)-ATPase with a simultaneous decrease in sodium intestinal transport and an increase in potassium absorption. Further differences in the behavior of the two electrolytes were observed when the concentration of sodium in the perfusates was altered. No changes occurred in amino acid or glucose transport in experimental animals.
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PMID:Inhibition of sodium intestinal transport and mucosal (Na+-K+)-ATPase in experimental Fanconi syndrome. 12 60

The relationship between lysozyme and sodium reabsorption by the kidney tubule was studied in the experimental Fanconi syndrome. Female, anesthetized Sprague-Dawley rats were injected intravenously with maleic acid (an inhibitor of sodium transport) neutralized with sodium hydroxide in doses of either 2 or 8 mmol/kg. Clearance studies were performed immediately afterward, and plasma and urine were analyzed for inulin, pH, sodium, glucose, and lysozyme. Two hours after the maleic acid injection, renal cortical tissue was removed and homogenized. Specific activity of Na-K-ATPase was assayed in the light microsomal fraction. The results showed that both concentrations of maleic acid caused significant increases in urinary volume, glucose excretion, and pH. There were significantly correlated decreases in TNafract and TLyfract. The slope of the regression line (TLyfract = 1.03 TNafract - 5.82; r = 0.92) approximated unity. Renal cortical Na-K-ATPase activity was significantly decreased by 25% in the animals receiving 2 mmol maleic acid and 43% in the animals receiving 8 mmol. The evidence suggests that lysozyme reabsorption in the proximal tubule might be mediated directly or indirectly by active tubular transport of sodium, a process that is related to the Na-K-ATPase transport system.
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PMID:Renal handling of lysozyme in experimental Fanconi syndrome. 14 77

Susceptibility of human skin fibroblasts to SV40 virus infection has been suggested as a marker of cancer risk. To evaluate the role of heritable factors in the regulation of SV40 T-antigen, fibroblasts from 9 pairs of identical twins and 129 members of cancer-prone families, including 16 with cancer, were tested in a 3-day immunofluorescence assay. In the twin study, the variance of T-antigen values was significantly less in identical than in fraternal or non-twin sibs, suggesting a heritable component in the regulation of SV40 infection. In the families, T-antigen values of parents and children were compared to models of Mendelian inheritance. At least three modes of inheritance--autosomal dominant, recessive, and X-linker--were observed. The distribution of offspring values compared to those of their parents suggested that interaction of multiple genetic factors influences the T-antigen value in individual patients. With the exception of Fanconi's anemia, the values for patients with cancer or predisposing syndromes were not uniformly elevated. The utility of this assay as a marker of cancer risk appears limited because of the complexity of factors that influence T-antigen expression in individual cases.
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PMID:Genetics of SV40 T-antigen expression: studies of twins, heritable syndromes and cancer families. 21 68

A patient with excessive industrial exposure to silicon and an elevated silicon content in his renal tissue was found to have a distinctive nephropathy, characterized pathologically by changes in the glomeruli and proximal tubules, and manifested clinically by albuminuria and hypertension. Proximal tubular function was intact. From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase).
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PMID:Silicon nephropathy. 113 57

Cellular cystine loading with cystine dimethyl ester inhibits volume absorption, transepithelial potential difference, glucose transport, and bicarbonate transport in proximal convoluted tubules perfused in vitro. This study examined the roles of ATP and NaK ATPase in this in vitro model of the Fanconi syndrome of cystinosis. Intracellular ATP was measured using the luciferin-luciferase assay. Intracellular ATP was reduced by 60% in proximal convoluted tubules incubated with 0.5 mM cystine dimethyl ester for 15 min at 37 degrees C (P less than 0.001). Incubation of cystine loaded tubules with 1 mM exogenous ATP increased intracellular ATP to levels not significantly different than that of controls. On the other hand, Vmax NaK ATPase activity was unchanged even though the incubation times and the concentration of cystine dimethyl ester were doubled to 30 min and 1 mM, respectively. In proximal convoluted tubules perfused in vitro, 0.5 mM cystine dimethyl ester resulted in an 89% inhibition in volume absorption (0.81 +/- 0.14 to 0.09 +/- 0.09 nl/mm.min), while there was only a 45% inhibition in volume absorption (P less than 0.01) due to cellular cystine loading in the presence of 1 mM lumen and bath ATP (0.94 +/- 0.05 to 0.52 +/- 0.11 nl/mm.min). These data demonstrate that proximal tubule cellular cystine loading decreases cellular ATP concentration, but does not directly inhibit NaK ATPase activity. The inhibition in transport and decrease in intracellular ATP due to cellular cystine loading was ameliorated by exogenous ATP. These data are consistent with cellular ATP depletion playing a major role in the inhibition of proximal tubule transport due to intracellular cystine loading.
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PMID:Role of adenosine triphosphate (ATP) and NaK ATPase in the inhibition of proximal tubule transport with intracellular cystine loading. 184 41

The induction of mutants at the hypoxanthine-guanine phosphoribosyltransferase and Na+/K+ ATPase loci by photoaddition of two bifunctional psoralens was compared in normal and in Fanconi's anemia lymphoblasts from the genetic complementation group A. For the two loci, the frequency of mutants was significantly lower in Fanconi's anemia than in normal cells. This is true whether the data are expressed as a function of dose or as a function of survival level. It is suggested that the chromosomal instability characteristic of Fanconi's anemia is responsible for the cancer proneness rather than the mutability at the gene level.
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PMID:Mutagenic response of Fanconi's anemia cells from a defined complementation group after treatment with photoactivated bifunctional psoralens. 215 78

The potential role of trace metals in the pathogenesis of various disease states, especially of renal and cardiovascular disease, has been recognized increasingly. Moreover, altered membrane transport was recently incriminated to play a role in renal tubular syndromes, such as the Fanconi syndrome, as well as in the pathogenesis of volume dependent hypertension. We therefore investigated the possible in vitro effects of various trace metals on Na-K-ATPase, the biochemical correlate of active cellular transmembrane sodium and sodium-dependent transport. To more closely mimic the in vivo situation, we deliberately chose as enzyme source renal tissue homogenate, which may contain protective agents. Under these experimental conditions, the metals studied inhibited the enzyme quantitatively in the following order: Hg greater than Pb greater than Cd greater than Ur greater than Cu greater than Zn greater than Mn greater than Ba greater than Ni greater than Sr. Enzyme kinetic studies showed that Hg, Pb, and Cd competitively, and Cu noncompetitively, inhibited the enzyme. In general, Mg-ATPase was significantly less sensitive to the trace metals. Accumulation of these metals may present serious health hazards by producing a general defect in cell membrane transport. From the other metals studied, i.e., Mn, Ba, Ni and Sr, some may have toxic effects via other mechanisms, whereas some may exert a protective role against toxicity of other agents including metal ions.
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PMID:In vitro inhibition of Na-K-ATPase by trace metals: relation to renal and cardiovascular damage. 302 55

The generalized proximal tubular transport abnormalities comprising the Fanconi syndrome (glycosuria, generalized aminoaciduria, the proximal form of renal tubular acidosis, and increased renal clearance of phosphate, urate, calcium, magnesium, and potassium) may be ascribed to interference with "sodiumlinked" active transport. Evidence is presented that the majority of conditions known to cause Fanconi syndrome in man or experimental animals are associated with inhibitors of the renal Na-K-ATPase-ATP transport system.
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PMID:Pathophysiology of human proximal tubular transport defects. 629 69

Ifosfamide (IF) is an alkylating cytostatic drug with urotoxic (hemorrhagic cystitis) and nephrotoxic side effects. Several cases of Fanconi syndrome in children following therapy with IF were reported. Little information is available concerning the pathomechanisms of transport inhibition by IF. We used a permanent renal epithelial cell line with proximal tubular characteristics (LLC-PK1) in order to investigate the effects of IF and some of its major metabolites (4-OH-IF, chloracetaldehyde, and acrolein). LLC-PK1 cells were used in a confluent state. Sodium-dependent and sodium-independent fluxes of 32PO4 were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria, and of endoplasmic reticulum were determined in cell homogenates. IF induces a moderate stimulation of PO4 transport. 4-OH-IF also has a stimulatory effect on transport at low concentrations (up to 200 mumol/l) and with short incubation (2h), while a 24-hour exposure of cells to 100 mumol/l of 4-OH-IF has an inhibitory effect of PO4 transport. Concentrations of 4-OH-IF which inhibit transport also reduce the activity of Na(+)-K(+)-ATPase. Chloracetaldehyde, like 4-OH-IF, induces a biphasic response of PO4 transport with stimulation in the low concentration range (up to 75 mumol/l) and inhibition at higher concentrations. Chloracetaldehyde reduces the activity of succinate-cytochrome c oxidoreductase, suggesting that a defect in ATP generation might play a role in the pathogenesis of Fanconi syndrome induced by IF. Acrolein strongly damages monolayers and reduces sodium-dependent transport of PO4 to very low levels at 150 mumol/l. It reduces the activities of both Na(+)-K+ ATPase and succinate-cytochrome c oxidoreductase. Acrolein also is the only metabolite with a moderate effect on alkaline phosphatase. We conclude that sodium-dependent transport of PO4 is highly sensitive to IF metabolites. In addition to direct toxic effects of IF metabolites on transport proteins within the apical plasma membrane, damage to mitochondrial enzymes and to Na(+)-K+ ATPase which generates the electrochemical gradients for secondary active PO4 transport may play an important role in the pathogenesis of Fanconi syndrome induced by IF.
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PMID:Effect of ifosfamide metabolites on sodium-dependent phosphate transport in a model of proximal tubular cells (LLC-PK1) in culture. 750 38


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