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)

In this study, we investigated the effects of endosomal alkalinization on kinetics of endocytotic uptake in intact proximal tubule-derived opossum kidney cells. We used fluorescein isothiocyanate (FITC)-labeled albumin and FITC-dextran as endocytotic substrates for receptor-mediated endocytosis and fluid-phase endocytosis, respectively. The pH in endosomes labeled with either FITC-albumin or FITC-dextran rose in the presence of the vacuolar-type ATPase inhibitor, bafilomycin A1, and in the presence of NH4Cl. Cytoplasmic pH, decreased in the presence of bafilomycin A1, but was not significantly different from control during prolonged exposure of the cells to NH4Cl. Endocytotic uptake of FITC-dextran was not affected by endosomal pH changes. Endocytotic uptake of FITC-albumin was reduced markedly by bafilomycin A1 (decrease of maximum transport rate and apparent affinity). Selective alkalinization of endosomes using NH4Cl (i.e., with the cytoplasmic pH not different from control) reduced FITC-albumin uptake in a similar way but to a lesser extent than did bafilomycin A1. Intracellular albumin degradation was impaired by bafilomycin A1 and NH4Cl. Prevention of endosome-lysosome fusion (lowering the temperature to 20 degrees C) abolished the effects of endosomal alkalinization. Furthermore, specific binding of albumin to the plasma membrane was reduced after incubation with bafilomycin A1, indicating an impairment of receptor recycling. These data show that endosomal pH is an important determinant for the kinetics of receptor-mediated endocytotic uptake of albumin in the proximal tubule but not for fluid-phase endocytosis. Endosomal alkalinization disturbs intracellular ligand handling and receptor trafficking, leading to a reduction of endocytotic capacity and affinity.
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PMID:Endosomal alkalinization reduces Jmax and Km of albumin receptor-mediated endocytosis in OK cells. 753 87

Vascular endothelial cells, which are polyfunctional, play an important role in the pathogenesis of diabetic complications. The increase in vascular permeability, ie, regulated by vascular endothelial cells, has been reported in patients with diabetes mellitus complicated by angiopathy. To determine the role of hyperglycemia in endothelial cell permeability, we examined the effect of high concentrations of glucose on the permeability of cultured bovine aortic endothelial cells. The permeations of albumin and fluorescein-labeled dextran (FD) across endothelial cell monolayers were increased when cultured with a high concentration of glucose (400 mg/dL). This increased permeation of albumin but not FD was temperature-dependent and was partially reduced by adding 100 mumol/L ponalrestat (ICI 128,436, Statil; ICI, Cheshire, UK), which is an aldose reductase inhibitor. Stimulation or inhibition of Na,K-adenosine triphosphatase (ATPase) in bovine aortic endothelial cells failed to alter their permeability. These findings suggest that high concentrations of glucose enhance transendothelial permeability of albumin in part by activating the polyol pathway, but independently of Na,K-ATPase activity.
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PMID:Increased transendothelial permeation of albumin by high glucose concentration. 754 Feb 48

Lung liquid clearance, epithelial permeability for Na+, mannitol and albumin, as well as Na,K-ATPase activity in alveolar type 2 (AT2) cells were studied during the acute and the recovery phase of hyperoxic lung injury. Rats exposed to 100% oxygen for 64 h were studied at 0, 7 and 14 d after removal from the hyperoxic chamber and compared with control rats breathing room air. In the isolated-perfused, liquid-filled rat lung, the albumin flux from the perfusate into the air spaces increased immediately after the oxygen exposure (220 +/- 56 mg/h) and returned to control values (28 +/- 7 mg/h) after 7 and 14 d of recovery. The small solutes (Na+ and mannitol) flux across the alveolar epithelium normalized only after 14 d of recovery in room air. Active Na+ transport and lung liquid clearance were reduced by approximately 45% immediately after oxygen exposure when compared with control values, increased by approximately 56% above control values after 7 d of recovery, and returned to control values after 14 d of recovery. Paralleling these changes the Na,K-ATPase activity decreased by approximately 41% in AT2 cells isolated from rats after 64 h of breathing 100% O2 and increased by approximately 25% after the rats recovered in room air for 7 d. These results suggest that alveolar epithelial Na,K-ATPase may contribute in the recovery from the hyperoxic lung injury by participating in the clearance of lung edema.
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PMID:Lung liquid clearance and Na,K-ATPase during acute hyperoxia and recovery in rats. 755 75

The effects of non-esterified arachidonic acid (AA) on erythrocyte membrane ion permeability have been studied using 86Rb flux measurements. [14C]AA was used to quantify membrane incorporation of AA and to show AA removal by albumin washing. The actions of vitamin E and other antioxidants on the effects of AA were examined. Reversible membrane incorporation of 700-2000 nmol AA per ml cells was achieved without significant haemolysis or morphological change. AA incorporation caused a reversible mean increase in bumetanide-sensitive Rb influx of 34% (S.E.M. 4.5, n = 23). This action could be partially prevented by co-incubation with vitamin E, but not by Trolox or dithioerythritol. AA incorporation caused an irreversible mean increase in residual Rb permeability (bumetanide and ouabain insensitive) of 130% (S.E.M. 22, n = 20), associated with a rise in intracellular Na and a fall in intracellular K concentrations. This action was also partially prevented by co-incubation with vitamin E. The effects of AA incorporation on Na,K-ATPase function were difficult to quantify because of the concomitant rises in intracellular Na but the data are consistent with approximately 20% inhibition of activity. Modulation of membrane ion permeability by AA appears to be partially mediated by lipid peroxidation and may have pathophysiological significance.
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PMID:Actions of arachidonic acid on erythrocyte membrane Rb permeability. 758 78

A lower concentration of intracellular myo-inositol has been implicated in the development of diabetic nephropathy. This was based on short-term studies showing that early administration of aldose reductase inhibitors or myo-inositol supplementation reduces increased glomerular filtration rate and partly reduces increased urinary albumin excretion in streptozotocin diabetic rats. We studied the effect of long-term (4 months) administration of 1% myo-inositol supplement to the Cohen diabetic (type 2) rat on the development of nephropathy and renal Na(+)-K(+)-ATPase. This treatment reduced the increased renal Na(+)-K(+)-ATPase activity but had no effect on blood glucose levels, body weight, increased kidney weight, or creatinine clearance and did not prevent or reduce the development of renal glomerular pathology. There was no correlation between the level of Na(+)-K(+)-ATPase activity and the degree of nephropathy. It is possible that the renal pathological changes are due to metabolic and humoral factors resulting from hyperglycaemia, other than myo-inositol depletion. The fact that myo-inositol treatment had no effect on the development of renal pathological changes but was shown to have a beneficial effect on restoring impaired conduction velocity and on the disruption of structural elements in the nerve indicates that the effect of the biological changes ensuing from hyperglycaemia vary in different tissues depending on local conditions.
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PMID:Effect of myo-inositol supplementation on the development of renal pathological changes in the Cohen diabetic (type 2) rat. 758 74

Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/potassium flux (at 1 degree C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268 +/- 99 and 299(277-465), respectively, vs. 166 +/- 65 mumol/(1 cells x h)] and was positively correlated (r = 0.36, P < 0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P < 0.001) in erythrocytes from diabetic patients compared with control subjects (1,196 +/- 276 vs. 833 +/- 253 mumol/l cells and 353 +/- 97 vs. 255 +/- 64 mumol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A1c (r = 0.39, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes. 766 4

Clinical manifestations of leptospirosis include disorders of the electrolytical balance which might be related to inhibition of Na,K-ATPase. Although the physiopathological cellular mechanism of leptospirosis remains unknown, a bacterial endotoxin has been incriminated. Therefore, we evaluated whether a glycolipoprotein fraction extracted from Leptospira interrogans and known to be cytotoxic might inhibit Na,K-ATPase. This glycolipoprotein fraction (GLP) inhibited Na,K-ATPase activity in rabbit kidney epithelial cells as well as Na,K-ATPase purified from rabbit kidney medulla. Inhibition was dose-dependent, and at maximum it almost abolished Na,K-ATPase activity whereas it had no effect on other enzymes. The GLP did not change the apparent affinity of Na,K-ATPase for potassium whereas it increased that for sodium, revealing a mechanism of inhibition different from that of ouabain. Finally, the inhibitory principle present in the GLP preparation was thermostable and was curtailed by the presence of albumin. In conclusion, a glycolipoproteic fraction extracted from Leptospira interrogans contains a specific inhibitor of Na,K-ATPase. This glycolipoproteic fraction which is present in diseased tissues might induce, through this inhibitor, cellular dysfunctions responsible for the symptoms, in particular those associated with electrolytical disorders such as disturbances of renal electrolyte handling, cardiac arrhythmia or diarrhoea.
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PMID:Inhibition of Na,K-ATPase by an endotoxin extracted from Leptospira interrogans: a possible mechanism for the physiopathology of leptospirosis. 767 Oct 8

The cells derived from the human embryo liver tissue were transfected with a plasmid pSV3neo containing both the large and small T-antigen gene of the early region of simian virus 40 (SV40), and two cell strains, OUMS-21 and -22, were obtained. OUMS-22 cells, to date, have reached over 100 population doublings through a culture crisis and are considered to have become an immortal cell line. However, OUMS-21 cells failed to become an immortal cell line. Both OUMS-21 and -22 cells were SV40 T-antigen-positive, epithelial-like, and immunoreactive against an anti-keratin 18 monoclonal antibody but against neither an anti-vimentin nor an anti-von Willebrandt factor VIII monoclonal antibody. The staining pattern of cytokeratin in these cells was similar to that in the differentiated human hepatoblastoma and hepatocellular carcinoma cell lines but not to that in the human cholangiocellular carcinoma cell lines. OUMS-21 and -22 cells expressed neither alpha-fetoprotein nor albumin mRNAs. These cells showed no tyrosine aminotransferase activity. However, both OUMS-21 and -22 cells were sensitive to cytotoxicity of aflatoxin B1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and benzo[a]pyrene, whereas human embryo lung fibroblasts were insensitive to the cytotoxicity of these carcinogens. These findings suggest that OUMS-21 and -22 cells may arise from undifferentiated liver stem cells or from hepatocytes that lost their ability to express the liver-specific functions prior to immortalization. Both OUMS-21 and -22 cells expressed glutathione S-transferase pi (GST-pi) mRNA. The expression of GST-pi mRNA highly increased in OUMS-22 cells with their immortalization. Karyotypic analysis showed that numerical and structural aberrations of the chromosomes were profound, but neither specific events nor marker chromosomes were found in OUMS-21 and -22 cells. Both OUMS-21 and -22 cells could grow in soft agar, but they were not tumorigenic when transplanted into nude mice.
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PMID:Immortalization of epithelial-like cells from human liver tissue with SV40 T-antigen gene. 768 77

Sodium transport across the lung epithelium is predominantly effected by apical amiloride-sensitive Na+ channels and basolaterally located ouabain-sensitive Na,K-ATPases. Previously, we reported that subacute hyperoxia caused an increase in active Na+ transport in rat lungs paralleling Na,K-ATPase upregulation in alveolar Type 2 cells isolated from the same lungs. In the present study we set out to quantify the amiloride-sensitive Na+ flux and ouabain-sensitive active Na+ transport in the isolated-perfused, fluid-filled lung model from rats exposed to 85% O2 for 7 d compared with normoxic control rats. We found increased transpulmonary albumin flux and permeability to small solutes (Na+ and mannitol) in hyperoxic rat lungs compared with controls. Amiloride (10(-5) M) instilled into rat airspaces inhibited active Na+ transport by approximately 62% in control rat lungs and by approximately 87% in lungs from rats exposed to hyperoxia, without further changing permeability for Na+ and mannitol. Ouabain (10(-5)M) perfused through the pulmonary circulation decreased active Na+ transport by approximately 40% in normal rat lungs and by approximately 52% in lungs from rats exposed to hyperoxia. We conclude that active Na+ transport and edema clearance are increased in the subacute hyperoxic lung injury in rats, caused in part by the upregulation of amiloride-sensitive apical Na+ channels and alveolar epithelial Na,K-ATPases. Conceivably, the upregulation of alveolar epithelial Na+ channels and Na,K-ATPases protects against the effects of lung injury in this model by contributing to effective edema clearance.
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PMID:Mechanisms of lung liquid clearance during hyperoxia in isolated rat lungs. 773 9

Cationic antiseptics--catamine AB, polysept (polymeric derivative of chlorhexidine) as well as cationic protein protamine exhibited a pronounced cytotoxic effect on human skin and lung fibroblasts in cell culture. Their effect was accompanied by augmentation of lipid peroxidation products and by inhibition of DT-diaphorase, LDH, ATPase and glutathione reductase. Introduction of alpha-tocopherol into the cultural medium normalized the rate of lipid peroxidation but did not remove the inhibitory effect on activity of oxidoreductase studied. Blood serum proteins immunoglobulins and albumin diminished significantly the cytotoxic effect of cationic preparations contributing to restoration of all the parameters studied to control values; this phenomenon appears to occur due to nonspecific membrane protective and antioxidation effects of the blood serum proteins.
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PMID:[Some biochemical indicators of the cytotoxic response of human fibroblasts cultured with natural and synthetic polycations]. 779 94


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