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)

Transport of lung liquid is essential for both normal pulmonary physiologic processes and for resolution of pathologic processes. The large internal surface area of the lung is lined by alveolar epithelial type I (TI) and type II (TII) cells; TI cells line >95% of this surface, TII cells <5%. Fluid transport is regulated by ion transport, with water movement following passively. Current concepts are that TII cells are the main sites of ion transport in the lung. TI cells have been thought to provide only passive barrier, rather than active, functions. Because TI cells line most of the internal surface area of the lung, we hypothesized that TI cells could be important in the regulation of lung liquid homeostasis. We measured both Na(+) and K(+) (Rb(+)) transport in TI cells isolated from adult rat lungs and compared the results to those of concomitant experiments with isolated TII cells. TI cells take up Na(+) in an amiloride-inhibitable fashion, suggesting the presence of Na(+) channels; TI cell Na(+) uptake, per microgram of protein, is approximately 2.5 times that of TII cells. Rb(+) uptake in TI cells was approximately 3 times that in TII cells and was inhibited by 10(-4) M ouabain, the latter observation suggesting that TI cells exhibit Na(+)-, K(+)-ATPase activity. By immunocytochemical methods, TI cells contain all three subunits (alpha, beta, and gamma) of the epithelial sodium channel ENaC and two subunits of Na(+)-, K(+)-ATPase. By Western blot analysis, TI cells contain approximately 3 times the amount of alphaENaC/microg protein of TII cells. Taken together, these studies demonstrate that TI cells not only contain molecular machinery necessary for active ion transport, but also transport ions. These results modify some basic concepts about lung liquid transport, suggesting that TI cells may contribute significantly in maintaining alveolar fluid balance and in resolving airspace edema.
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PMID:Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis. 1184 14

Short (<1 sec) duration depolarization of Xenopus laevis oocytes to voltages greater than +40 mV activates a sodium-selective channel (Na(x)) with sodium permeability five to six times greater than the permeability of other monovalent cations examined, including K+, Rb+, Cs+, TMA+, and Choline+. The permeability to Li+ is about equal to that of Na+. This channel was present in all oocytes examined. The kinetics, voltage dependence and pharmacology of Na(x)distinguish it from TTX-sensitive or epithelial sodium channels. It is also different from the sodium channel of Xenopus oocytes activated by prolonged depolarization, which is more highly selective for Na+, requires prolonged depolarization to be activated, and is blocked by Li+. Intracellular Mg2+ reversibly inhibits Na(x), whereas extracellular Mg2+ does not have an inhibitory effect. Intracellular Mg2+ inhibition of Na(x), is voltage dependent, suggesting that Mg2+ binding occurs within the membrane field. Eosin is also a reversible voltage-dependent intracellular inhibitor of Na(x), suggesting that a P-type ATPase may mediate the current. An additional cytoplasmic factor is involved in maintaining Na(x) since the current runs down in internally perfused oocytes and excised membrane patches. The rundown is reversible by reintroduction of the membrane patch into oocyte cytoplasm. The cytoplasmic factor is not ATP, because ATP has no effect on Na(x) current magnitude in either cut-open or inside-out patch preparations. Extracellular Gd3+ is also an inhibitor of Na(x). Na(x) activation follows a sigmoid time course. Its half-maximal activation potential is +100 mV and the effective valence estimated from the steepness of conductance activation is 1.0. Na(x) deactivates monoexponentially upon return to the holding potential (-40 mV). The deactivation rate is voltage dependent, increasing at more negative membrane potentials.
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PMID:Properties of a sodium channel (Na(x)) activated by strong depolarization of Xenopus oocytes. 1189 81

The discovery of mechanisms that regulate salt and water transport by the alveolar and distal airway epithelium of the lung has generated new insights into the regulation of lung fluid balance under both normal and pathological conditions. There is convincing evidence that active sodium and chloride transporters are expressed in the distal lung epithelium and are responsible for the ability of the lung to remove alveolar fluid at the time of birth as well as in the mature lung when pathological conditions lead to the development of pulmonary edema. Currently, the best described molecular transporters are the epithelial sodium channel, the cystic fibrosis transmembrane conductance regulator, Na+-K+-ATPase, and several aquaporin water channels. Both catecholamine-dependent and -independent mechanisms can upregulate isosmolar fluid transport across the distal lung epithelium. Experimental and clinical studies have made it possible to examine the role of these transporters in the resolution of pulmonary edema.
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PMID:Lung epithelial fluid transport and the resolution of pulmonary edema. 1208 29

Alendronate, an aminobisphosphonate, produces as a side effect a topical (pill induced) esophagitis. To gain insight into this phenomenon, we assessed the effects of luminal alendronate on both esophageal epithelial structure and function. Sections of rabbit esophageal epithelium were exposed to luminal alendronate at neutral or acidic pH while mounted in Ussing chambers to monitor transmural electrical potential difference (PD), short-circuit current (I(sc)), and resistance (R). Morphological changes were sought by light microscopy in hematoxylin and eosin-stained sections. Impedance analysis was used for localization of alendronate-induced effects on ion transport. Luminal, but not serosal, alendronate (pH 6.9-7.2), increased PD and I(sc) in a dose- and time-dependent manner, with little change in R and mild edema of surface cell layers. The changes in I(sc) (and PD) were reversible with drug washout and could be prevented either by inhibition of Na,K-ATPase activity with serosal ouabain or by inhibition of apical Na channels with luminal acidification to pH 2.0 with HCl. An effect on apical Na channel activity was also supported by impedance analysis. Luminal alendronate at acidic pH was more damaging than either alendronate at neutral pH or acidic pH alone. These data suggest that alendronate stimulates net ion (Na) transport in esophageal epithelium by increasing apical membrane sodium channel activity and that this occurs with limited morphological change and no alteration in barrier function. Also alendronate is far more damaging at acidic than at neutral pH, suggesting its association with esophagitis requires gastric acid for expression. This expression may occur either by potentiation between the damaging effects of (refluxed) gastric acid and drug or by acid-induced conversion of the drug to a more toxic form.
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PMID:Physiological and morphological effects of alendronate on rabbit esophageal epithelium. 1218 Nov 70

A function of the transcription factor REST is to block the expression of neuronal phenotypic traits in non-neuronal cells. Previous studies have shown that REST-mediated repression requires histone deacetylase activity and that recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST. In this study, we show that a repressor domain in CoREST interacts with BRG1-associated factor (BAF) 57, a component of the hSWI.SNF complex. In vivo, BAF57 occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other members of the hSWI.SNF complex, are also present in the REST.CoREST repressor complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170 into Rat1 fibroblasts relieves repression of RE1 reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression.
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PMID:REST repression of neuronal genes requires components of the hSWI.SNF complex. 1219

The mechanisms of acute copper and silver toxicity in freshwater organisms appear similar. Both result in inhibition of branchial sodium (and chloride) uptake initiating a cascade of effects leading to mortality. The inhibition of the branchial Na/K-ATPase in the basolateral membrane is generally accepted as the key component responsible for the reduced sodium uptake. We propose that branchial carbonic anhydrase and the apical sodium channel may also be important targets for both copper and silver exposure. Several attempts have been made to predict metal sensitivity. A prominent example is the geochemical-biotic ligand model. The geochemical-biotic ligand modeling approach has been successful in explaining variations in tolerance to metal exposure for specific groups of animals exposed at different water chemistries. This approach, however, cannot explain the large observed variation in tolerance to these metals amongst different groups of freshwater animals (i.e. Daphnia vs. fish). Based on the detailed knowledge of physiological responses to acute metal exposure, the present review offers an explanation for the observed variation in tolerance. Smaller animals are more sensitive than large animals because they exhibit higher sodium turnover rates. The same relative inhibition of sodium uptake results in faster depletion of internal sodium in animals with higher sodium turnover. We present a way to improve predictions of acute metal sensitivity, noting that sodium turnover rate is the key predictor for variation in acute copper and silver toxicity amongst groups of freshwater animals. We suggest that the presented sodium turnover model is used in conjunction with the Biotic Ligand Model for risk management decisions.
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PMID:Sodium turnover rate determines sensitivity to acute copper and silver exposure in freshwater animals. 1235 34

To investigate the relationship between 12 candidate genes responsible for water regulation, sodium metabolism and membrane ion transport and essential hypertension (EH) in the Chinese. Linkage analysis of EH was performed in 95 Chinese nuclear families including 477 subjects using a technique of fluorescence-based gene scanning with 12 microsatellite markers. Markers were selected on the chromosomal regions covering 12 candidate genes responsible for regulating water and sodium metabolism and membrane ion transport. These candidate genes included sodium hydrogen exchanger 3, sodium hydrogen exchanger 5, chloride bicarbonate exchanger 3, sodium calcium exchanger 1, mineralocorticoid receptor, plasma membrane calcium ATPase 2, ATPase,Na/K transporting alpha, a-adducin, SA gene, kidney epithelial sodium channel-gamma, vasopressin receptor 1A, and 11beta-hydroxysteroid dehydrogenase type 2 genes. Two-point non-parametric linkage analysis (NPL), maximum LOD score analysis and transmission/disequilibrium test (TDT) were performed using the GENEHUNTER software package. The NPL analysis and LOD score suggested a significant linkage at D12S398 (Z = 2.08, p<0.05 and LOD score = 1.26, p<0.01, respectively). TDT indicated a significant disequilibrium of transmission at the locus chi2 = 9.00, p < 0.005). No significant linkages were found at the other loci tested (p > 0.05 or LOD < -1). In conclusion, D12S398, a marker near the vasopressin receptor 1A gene (V1AR), showed a positive linkage with EH based on the results of three statistical methods (NPL, LOD score, and TDT). This region warrants further exploration.
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PMID:Linkage analysis of twelve candidate gene loci regulating water and sodium metabolism and membrane ion transport in essential hypertension. 1235 53

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride-insensitive short circuit current (I(sc)) and Na(+)-K(+) ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl(-) transport or cGMP-gated cation channels had a significant (P < 0.05), but limited ability to block the increased I(sc). EF increased amiloride-insensitive, but not amiloride-sensitive, DLE apical membrane Na(+) conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (alpha, beta), or decreased (gamma, P < 0.05) in EF-exposed DLE. EF also induced an amiloride-insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild-type and alpha-ENaC-deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride-insensitive I(sc) in DLE and liquid absorption by distal lung explants. Thus proteins or protein-dependent factors within cardiogenic EF induce an alpha-ENaC-independent and amiloride-insensitive apical membrane Na(+) conductance and liquid absorption in the distal lung.
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PMID:Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na(+) transport and fluid absorption in the distal lung. 1238 7

Hypoxia reduces alveolar liquid clearance and the nasal potential difference, a marker of airway epithelial sodium transport. The mechanisms underlying this impaired epithelial sodium transport in vivo remain uncertain. We hypothesized that epithelial sodium transport impaired by hypoxia would recover quickly with reoxygenation and that hypoxia decreases the expression of lung epithelial sodium channels and Na,K-ATPases. We studied adult rats exposed to normoxia, hypoxia (Fi(O(2)) = 0.1) for 24 h, or hypoxia followed by recovery in normoxia. Nasal potential differences decreased by 40% with hypoxia (P < 0.001), returning to baseline levels with reoxygenation. Lung Na,K-ATPase activity decreased by 40% with hypoxia (P = 0.003), recovering to baseline levels with reoxygenation. Lung expression of mRNA encoding for epithelial sodium channel (ENaC)-alpha, -beta, and -gamma or for Na,K-ATPase-alpha(1) did not change significantly with hypoxia or recovery nor did lung expression of ENaC-alpha, ENaC-beta, Na,K-ATPase-alpha(1), or Na,K-ATPase-beta(1) protein. We conclude that subacute exposure to moderate hypoxia reversibly impairs airway epithelial sodium transport and lung Na,K-ATPase activity but that those changes are not due to changes in the lung expression of sodium-transporting proteins.
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PMID:Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expression. 1238 31

The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na+ transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na+/H+ exchanger (NHE3), Na+ - K+-ATPase, the bumetanide-sensitive Na+ - K+ - 2Cl- cotransporter (BSC-1), the thiazide-sensitive Na+ - Cl- cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na+ loss and/or to maintain intracellular pH levels.
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PMID:Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. 1238 87


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