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)

Evidence based on the following three observations suggests the existence of a calcium transport system in the mammalian lens: calcium levels in the lens are lower than that measured in the aqueous humor; calcium efflux is temperature-dependent and is reduced by inhibitors of Ca++ transport; and there exists a calcium-acivated, magnesium-dependent ATPase. In rat, bovine, dog, and rabbit lenses, the concentration of total calcium was found to be approximately 0.2 mM, at least an order of magnitude lower than that found in the aqueous humor. To determine the nature of the mechanism responsible for maintaining these low levels, calcium fluxes were measured. During the initial rapid phase of 45Ca efflux, the rate at 4 degrees C was reduced by 85% compared with that found at 37 degrees C. Efflux was not altered in the absence of external Na+. Calcium efflux was reduced, however, by lanthanum and propranolol, inhibitors of Ca/Mg ATPase. The presence of Ca/Mg ATPase was also demonstrated in the rat, bovine, and rabbit lens and was likewise inhibited by both lanthum and propranolol.
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PMID:Calcium transport in the lens. 644 74

The vertebrate corneal endothelium represents a unique model system for investigating many cellular aspects of wound repair within an organized tissue in situ. The tissue exists as a cell monolayer that resides upon its own natural basement membrane that can be prepared as a flat mount to observe the entire cell population. Thus, it readily avails itself to many cytological and immunocytochemical methods at both the light microscopic and ultrastructural levels. In addition, the tissue is easily explanted into organ culture where further investigations can be carried out. These techniques have enabled investigators to use many approaches to explore function and changes in response to injury. In vivo, the endothelium acts as a transport tissue to actively pump Na+ and bicarbonate ions from the corneal stroma into the aqueous humor to control corneal transparency. Physiological findings indicate that fluid diffuses back into the stroma, across the endothelium, and thus hydration is said to be controlled by a pump-leak mechanism. Ultrastructural investigations, some employing horseradish peroxidase and lanthanum, have established the morphological basis for this mechanism as apical focal junctions that are not the classical tight junctions and do not constitute a complete zona occludens. Along with these apical focal junctions are gap junctions that appear identical to their counterparts in other cell types. Cytochemical studies localized both Na+K(+)-ATPase and carbonic anhydrase, the main pump enzymes associated with corneal hydration, to the lateral plasma membranes. Corneal endothelial cells of noninjured tissue do not traverse the cell cycle and are considered to be in the "Go" phase of the cell cycle as determined by microfluorometric analysis with DNA binding dyes such as auramin O and pararosaniline-Feulgen. However, injury can initiate cell cycle transverse and histochemical and cytological methods have been used to understand the tissue's response. Classical histochemical studies revealed that increased staining was observed for metabolic (NADase and NADPase) and lysosomal enzymes in cells bordering the wound area. The use of radiolabelled agents has further lead to an understanding of the endothelial wound response. Autoradiographic analyses of 3H-actinomycin D incorporation indicated that injury initiates changes in chromatin leading to increased binding levels of the drug in cells surrounding the wound. This change suggests that those cells undergo heightened macromolecular synthesis and this was confirmed by examining 3H-uridine and 3H-thymidine incorporation. The major mechanism involved in corneal endothelial repair is cell migration. Cytochemical and immunocytochemical investigations have allowed investigators an opportunity to gain some insight into changes that occur during this cellular process.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytological and immunocytochemical approaches to the study of corneal endothelial wound repair. 805 65

We used an animal model of hypocalcemic cataract to investigate the changes of the cation levels and the Ca2+ pump (Ca(2+)-ATPase) function in the lens. Wistar rats (4 weeks old) were fed with a low calcium and no vitamin D3 diet. After 4 weeks on this diet, anterior subcapsular cataract was recognized, when calcium concentration in the aqueous humor and serum had significantly decreased. Calcium content in the lens decreased and sodium content increased. Ca(2+)-ATPase activity detected by [gamma-32P] ATP assay did not show significant change. We concluded that cataract during the early stage of hypocalcemia is caused by membrane damage with low calcium level in the aqueous humor and sodium content increase in the lens. We also studied the ultracytochemical localization of Ca(2+)-ATPase activity and found it in the plasma membrane of the lens epithelium and cortex and also in the epithelium organelles.
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PMID:[Ca(2+)-ATPase activity in the hypocalcemic cataract]. 810 58

It was reported previously that dietary ascorbate (ASC) delays the development of galactose-induced cataract in guinea pigs compared to the rate which is observed in ASC-deficient animals. Experiments were conducted to explore the possible mechanism of this phenomenon. Guinea pigs were fed for a period of up to 4 weeks either a normal diet (1 g ASC/kg diet) or a scorbutic diet (< 0.04 g ASC/kg diet) combined with 10% galactose in the drinking water. After 2 weeks, levels of ASC in animals on the scorbutic diet decreased by 95% in the aqueous humor and by 78% in the lens. Slit lamp examination showed that galactose-induced vacuoles in the lens equator formed at a significantly faster rate in the scorbutic animals. However, examination of biochemical parameters in whole lenses of the two groups of animals after 2 weeks showed no significant differences with regard to accumulation of galactose and galactitol, decreases in the levels of myoinositol, taurine and GSH or changes in cation concentrations. In order to examine possible regional changes in the lenses, various parameters were studied in the lens capsule-epithelium. On day 4, the capsule epithelia of scorbutic animals on a galactose diet had a content of galactitol two-and-a-half times higher than that of normal galactose-fed animals. Scorbutic conditions also intensified the loss of Na(+)-K+ ATPase activity in the lens capsule-epithelium caused by galactose feeding. Oxidized glutathione was not detectable in the lens capsule epithelia of any of the animals studied. Hexose monophosphate shunt activity was elevated in lenses of normal galactose-fed animals during the first hour of culture after death whereas lenses of scorbutic galactose-fed animals were not. Consistent with the in vivo findings, galactitol accumulation in dog lens epithelial cells exposed to 30 mM galactose was significantly inhibited by the presence of either ASC or dehydroascorbate (DHA) in the medium. Hexose monophosphate shunt activity in the cells was stimulated to two-and-a-half times its initial level by either 1 mM DHA or 30 mM galactose and slightly more than three-fold by a combination of the two challenges. The results suggest that decreased polyol accumulation in the lens epithelium of the normal galactose-fed guinea pig, which has a high level of ASC in the aqueous humor, accounts for the delay in onset of cataract compared to that for the ASC-deficient animal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A physiological level of ascorbate inhibits galactose cataract in guinea pigs by decreasing polyol accumulation in the lens epithelium: a dehydroascorbate-linked mechanism. 815 13

The mechanisms controlling the production of aqueous humor and the regulation of intraocular pressure are poorly understood. Here, we provide evidence that a vacuolar H+-ATPase (V-ATPase) in the ocular ciliary epithelium is a key component of this process. In intracellular pH (pHi) measurements of isolated ciliary epithelium performed with 2',7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), the selective V-ATPase inhibitor bafilomycin A1 slowed the recovery of pHi in response to acute intracellular acidification, demonstrating the presence of V-ATPase in the plasma membrane. In isolated rabbit ciliary body preparations examined under voltage-clamped conditions, bafilomycin A1 produced a concentration-dependent decrease in short-circuit current, and topical application of bafilomycin A1 reduced intraocular pressure in rabbits, indicating an essential role of the V-ATPase in ciliary epithelial ion transport. Immunocytochemistry utilizing antibodies specific for the B1 isoform of the V-ATPase 56-kDa subunit revealed localization of V-ATPase in both the plasma membrane and cytoplasm of the native ciliary epithelium in both rabbit and rat eye. The regional and subcellular distribution of V-ATPase in specific regions of the ciliary process was altered profoundly by isoproterenol and phorbol esters, suggesting that change in the intracellular distribution of the enzyme is a mechanism by which drugs, hormones, and neurotransmitters modify aqueous humor production.
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PMID:Vacuolar H+-ATPase in ocular ciliary epithelium. 919 37

Sodium-water balance is causally linked to the functional expression of a number of important ocular tissues, viz. corneal deturgescence, aqueous humor secretion by the iris, hydration of the lens, retinal photoreception, and choriocapillary angiogenesis. The regulation of sodium absorption in the eye is generally believed to be under the control of Na(+),K(+)-activated adenosine triphosphatase, although evidence for this view is at best circumstantial. Contemporary work has shown widespread distribution of the mineralocorticoid hormone receptor and its colocalization with the amiloride-sensitive sodium channel in cells of diverse embryological origins. All available evidence favors the idea that the transcriptional regulation of the apical sodium channel by adrenocorticoids, and not the basolateral sodium pump, is critically important to sodium-water homeostasis in various ocular tissues, in a manner previously believed to be limited exclusively to the epithelial cell in various peripheral organs. Based upon these parameters, models are presented to help in understanding the direction of sodium absorption in a number of ocular tissues. Thus, the regulation of the sodium channel by steroid hormones seems to be a universal feature of the living cell that may have important implications in the understanding and management of normal ocular functions and their modification in human pathology.
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PMID:Receptor-mediated adrenocorticoid hormone signaling in ocular tissues. 1269 62

Endothelin-1 (ET-1) (1-100 nM) decreases the activity of Na,K-ATPase, a key enzyme responsible for aqueous humor formation, in transformed human non-pigmented ciliary epithelial (HNPE) cells. The present study sought to determine if ET-1 alters the expression of the catalytically active alpha subunit of Na,K-ATPase in HNPE cells and identify mechanisms underlying these effects. We report that acute (15 and 30 min) treatment with ET-1 results in an increase in mRNA expression of the alpha 1 subunit of Na,K-ATPase. Similar to ET-1's effects, ouabain (100 microM), a selective inhibitor of Na,K-ATPase, and monensin (10 microM), a sodium ionophore, also increased Na,K-ATPase expression in HNPE cells. The increase in Na,K-ATPase expression by short-term treatment with ouabain and monensin was dependent on their ability to elevate intracellular sodium concentrations. However, acute ET-1 treatment mediated increase in Na,K-ATPase expression was independent of changes in intracellular sodium. A prolonged (24 hr) ET-1 treatment results in an increase in both mRNA and protein levels of the alpha 1 subunit of Na,K-ATPase. These observations suggest that ET-1 could play a homeostatic role in modulating aqueous humor formation by having differential effects on the activity and expression of Na,K-ATPase by the ciliary epithelium in the eye.
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PMID:Regulation of Na,K-ATPase expression by endothelin-1 in transformed human ciliary non-pigmented epithelial (HNPE) cells. 1458 38

1. We developed a novel method to isolate nonpigmented epithelial (NPE) cells from porcine eyes in order to examine Na,K-ATPase responses to nitric oxide (NO) donors specifically in the epithelium. 2. Cells were treated with NO donors and other test compounds for 20 min prior to Na,K-ATPase activity measurement. 3. NO donors, sodium nitroprusside (SNP, 1 microM-1 mM), sodium azide (100 nM-1 microM) and S-nitroso-N-acetylpenicillamine (1 microM-1 mM) caused significant concentration-dependent inhibition of Na,K-ATPase activity. Detection of nitrite in the medium of L-arginine and SNP-treated NPE confirmed NO generation. 4. Concentration-dependent inhibition of Na,K-ATPase was also obtained by L-arginine (1-3 mM), a physiological precursor of NO and 8p-CPT-cGMP (1-100 microM), a cell permeable analog of cGMP. The L-arginine effect was abolished when the NO synthesizing enzyme, NO-synthase, was inhibited by L-NAME (100 microM). 5. The inhibitory effect of SNP or sodium azide on Na,K-ATPase activity was suppressed by soluble guanylate cyclase (sGC) inhibitors, ODQ (10 microM) or methylene blue (10 microM). 6. The inhibitory effect of 8p-CPT-cGMP on Na,K-ATPase was abolished by protein kinase G (PKG) inhibitors, H-8 (1 microM) and H-9 (20 microM), but not by the protein kinase A (PKA) inhibitor H-89 (100 nM). H-8 and H-9 partially suppressed the inhibitory effect of SNP on Na,K-ATPase. 7. Taken together the results indicate that Na,K-ATPase inhibition response to NO donors involves activation of sGC, generation of cGMP and activation of PKG. These findings suggest that Na,K-ATPase inhibition in NPE may contribute to the ability of NO donors to reduce aqueous humor secretion.
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PMID:NO donors inhibit Na,K-ATPase activity by a protein kinase G-dependent mechanism in the nonpigmented ciliary epithelium of the porcine eye. 1677 Mar 22

The rate of aqueous humor formation sequentially across the pigmented (PE) and nonpigmented (NPE) ciliary epithelial cell layers may not be uniform over the epithelial surface. Because of the tissue's small size and complex geometry, this possibility cannot be readily tested by conventional techniques. Rabbit iris-ciliary bodies were divided, incubated, quick-frozen, cryosectioned, and freeze-dried for electron probe X-ray microanalysis of the elemental contents of the PE and NPE cells. We confirmed that preincubation with ouabain to block Na(+),K(+)-ATPase increases Na(+) and decreases K(+) contents far more anteriorly than posteriorly. The anterior and posterior regions were the iridial portion of the primary ciliary processes and the pars plicata, respectively. Following interruption of gap junctions with heptanol, ouabain produced smaller changes in anterior PE cells, possibly reflecting higher Na(+) or K(+) permeability of anterior NPE cells. Inhibiting Na(+) entry selectively with amiloride, benzamil, or dimethylamiloride reduced anterior effects of ouabain by approximately 50%. Regional dependence of net secretion was also assessed with hypotonic stress, which stimulates ciliary epithelial cell regulatory volume decrease (RVD) and net Cl(-) secretion. In contrast to ouabain's actions, the RVD was far more marked posteriorly than anteriorly. These results suggest that 1) enhanced Na(+) reabsorption anteriorly, likely through Na(+) channels and Na(+)/H(+) exchange, mediates the regional dependence of ouabain's actions; and 2) secretion may proceed primarily posteriorly, with secondary processing and reabsorption anteriorly. Stimulation of anterior reabsorption might provide a novel strategy for reducing net secretion.
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PMID:Electron microprobe analysis of rabbit ciliary epithelium indicates enhanced secretion posteriorly and enhanced absorption anteriorly. 1772 95

Intraocular pressure (IOP) is regulated by the resistance to outflow of the eye's aqueous humor. Elevated resistance raises IOP and can cause glaucoma. Despite the importance of outflow resistance, its site and regulation are unclear. The small size, complex geometry, and relative inaccessibility of the outflow pathway have limited study to whole animal, whole eye, or anterior-segment preparations, or isolated cells. We now report measuring elemental contents of the heterogeneous cell types within the intact human trabecular outflow pathway using electron-probe X-ray microanalysis. Baseline contents of Na(+), K(+), Cl(-), and P and volume (monitored as Na+K contents) were comparable to those of epithelial cells previously studied. Elemental contents and volume were altered by ouabain to block Na(+)-K(+)-activated ATPase and by hypotonicity to trigger a regulatory volume decrease (RVD). Previous results with isolated trabecular meshwork (TM) cells had disagreed whether TM cells express an RVD. In the intact tissue, we found that all cells, including TM cells, displayed a regulatory solute release consistent with an RVD. Selective agonists of A(1) and A(2) adenosine receptors (ARs), which exert opposite effects on IOP, produced similar effects on juxtacanalicular (JCT) cells, previously inaccessible to functional study, but not on Schlemm's canal cells that adjoin the JCT. The results obtained with hypotonicity and AR agonists indicate the potential of this approach to dissect physiological mechanisms in an area that is extremely difficult to study functionally and demonstrate the utility of electron microprobe analysis in studying the cellular physiology of the human trabecular outflow pathway in situ.
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PMID:Electron probe X-ray microanalysis of intact pathway for human aqueous humor outflow. 1875 14


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