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)

Ultrastructural localization of Na, K-ATPase alpha-subunit along rat nephron segments was investigated quantitatively by immunogold electron microscopy on LR-White ultrathin sections using affinity-purified antibody against alpha-subunit of the enzyme. Ultrathin sections were incubated with the antibody at a saturation level and the number of gold particles bound per micron of the plasma membrane (particle density) of the tubular epithelial cells from the proximal tubule to the collecting duct was determined. In all the tubular epithelial cells, gold particles were located exclusively on the basolateral surface, and no significant binding of gold particles to the apical surface was observed. Distribution of gold particles on the basolateral membranes was quite heterogeneous; lateral membranes and infolded basal membranes were highly labeled, whereas the basal membranes which are in direct contact with the basal lamina were scarcely labeled. The average particle density on the basal surface was highest in the distal straight tubule cells (11.4 units), very high in the distal convoluted tubule cells (9.8 units), intermediate in the proximal tubule cells (3.3 units), in the connecting tubule cells (4.3 units), and in the principal cells of the collecting duct (5.6-3.8 units), low in the thin limb of Henle's loop (1.0 unit), and at the control level in the intercalated cells in the connecting and collecting duct. The relative number of gold particles/mm nephron segment and the relative number of gold particles in the various nephron segments were calculated using quantitative morphological data. The estimated distribution profile of the former was in good agreement with the Na, K-ATPase activity profile in rat nephron, which was determined biochemically with a microenzymatic method.
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PMID:Quantitative immunogold localization of Na, K-ATPase along rat nephron. 133 63

The present study examined proximal tubular respiration in control proximal tubules and proximal tubules loaded with cystine using 2 mmol/L cystine dimethyl ester. Basal oxygen consumption was significantly less in cystine-loaded tubules (20.6 +/- 0.5 versus 12.1 +/- 0.6 nmol O2.min-1.mg protein-1, p < 0.001). In the presence of 10(-4) mol/L ouabain, an inhibitor of the NaK ATPase, oxygen consumption was 10.2 +/- 0.7 nmol O2.min-1.mg protein-1 in control tubules and 11.4 +/- 1.0 nmol O2.min-1.mg protein-1 in cystine-loaded tubules. Thus, proximal tubular intracellular cystine loading specifically inhibits oxygen metabolism directed toward transport. Compared with control proximal tubules, cystine-loaded proximal tubules also had a lower rate of O2 consumption when the cells were permeabilized to sodium with nystatin and when mitochondrial respiration was uncoupled. Glycine, an amino acid that is cytoprotective to hypoxic proximal tubule injury, ameliorated the respiratory dysfunction observed in cystine-loaded tubules.
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PMID:Intracellular cystine loading causes proximal tubule respiratory dysfunction: effect of glycine. 133 87

Monolayers of human proximal tubule (HPT) cells, when grown on permeable supports and mounted in Ussing chambers, spontaneously display a transepithelial potential difference (PD) and short-circuit current (Isc). These electrical parameters were used in the present study to determine if aminoglycoside exposure altered electrogenic sodium transport by HPT cells. The results of this determination demonstrated that exposure to gentamicin, at levels below that producing cell necrosis, caused a marked reduction in Isc and that this reduction followed the known in vivo nephrotoxicities of the aminoglycosides streptomycin, gentamicin, and neomycin. It was concluded through a similar analysis on a total of 14 isolates of HPT cells that the aminoglycosides repeatably reduced the electrogenic sodium transport of HPT cells. It was further determined that this alteration in electrogenic transport by gentamicin was mediated through exposure of the drug to the basolateral cell surface and that apical exposure had little effect. Evidence was obtained against the involvement of Na+, K(+)-ATPase, adenosine 3',5'-cyclic monophosphate, and sodium-coupled substrate transport in this alteration in electrogenic transport by the aminoglycosides. The basolaterally located Na+: CO3(-2):HCO3(-1) symporter is a possible site for aminoglycoside-induced nephrotoxicity.
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PMID:Aminoglycoside antibiotics alter the electrogenic transport properties of cultured human proximal tubule cells. 133 17

The intercalated cells of the kidney collecting duct are specialized for physiologically regulated proton transport. In these cells, a vacuolar H(+)-ATPase is expressed at enormous levels in a polarized distribution on the plasma membrane, enabling it to serve in transepithelial H+ transport. In contrast, in most eukaryotic cells, vacuolar H(+)-ATPases reside principally in intracellular compartments to effect vacuolar acidification. To investigate the basis for the selective amplification of the proton pump in intercalated cells, we isolated and sequenced cDNA clones for two isoforms of the approximately 56-kDa subunit of the H(+)-ATPase and examined their expression in various tissues. The predicted amino acid sequence of the isoforms was highly conserved in the internal region but diverged in the amino and carboxyl termini. mRNA hybridization to a cDNA probe for one isoform (the "kidney" isoform) was detected only in kidney cortex and medulla, whereas mRNA hybridization to the other isoform of the approximately 56-kDa subunit and to the H(+)-ATPase 31-kDa subunit was found in the kidney and other tissues. Immunocytochemistry of rat kidney with an antibody specific to the kidney isoform revealed intense staining only in the intercalated cells. Staining was absent from proximal tubule and thick ascending limb, where H(+)-ATPase was detected with a monoclonal antibody to the 31-kDa subunit of the H(+)-ATPase. This example of specific amplification of an isoform of one subunit of the vacuolar H(+)-ATPase being limited to a specific cell type suggests that the selective expression of the kidney isoform of the approximately 56-kDa subunit may confer the capacity for amplification and other specialized functions of the vacuolar H(+)-ATPase in the renal intercalated cell.
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PMID:Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56-kilodalton subunit in renal intercalated cells. 137 1

Studies from this laboratory demonstrate that LLC-PK1/Cl4 cells, a cultured renal cell line, respond to incubation in low-K+ medium by coordinately increasing abundance of both alpha- and beta-subunits of Na(+)-K(+)-ATPase but increase only beta- and not alpha-mRNA levels (Lescale-Matys et al. J. Biol. Chem. 265: 17935-17940, 1990) and that alpha-abundance is likely increased as a result of increased efficiency of alpha-mRNA translation (L. Lescale-Matys and A. A. McDonough. J. Cell Biol. 111: 311A, 1990). The aim of this report was to determine if nontransformed kidney cells would respond to low K+ in a similar manner. We incubated primary cultures of rat proximal tubule cells in low K+ (0.25 mM) for up to 24 h to address this aim. Na(+)-K(+)-ATPase activity, measured enzymatically, and abundance of alpha- and beta-subunits, measured by immunoblot, were increased significantly and coordinately by 8 h of low K+, and, by 24 h of low K+, these parameters were increased to 2.17 +/- 0.34 (activity), 2.03 +/- 0.21 (alpha), and 2.39 +/- 0.48 (beta)-fold over control. Pretranslationally, beta-mRNA, measured by Northern blot analysis, increased to 1.76 +/- 0.35 after 3 h of low K+ and to 3.4 +/- 0.75-fold over control after 24 h of low K+. The increase in alpha-mRNA was smaller and delayed compared with the beta-mRNA response, but it was sufficient to account for the observed increase in alpha-protein and Na(+)-K(+)-ATPase activity at steady state: alpha-mRNA increased to 1.27 +/- 0.09 after 6 h and to 1.91 +/- 0.41-fold over control after 24 h in low K+. We conclude that the accumulation of sodium pumps in cultured renal proximal tubule cells, unlike LLC-PK1 cells, can be accounted for by increases in both alpha- and beta-subunit mRNA levels.
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PMID:Low K+ increases Na(+)-K(+)-ATPase alpha- and beta-subunit mRNA and protein abundance in cultured renal proximal tubule cells. 138 Nov 48

Distal urinary acidification abnormalities may arise from transepithelial voltage defects, permeability defects, or proton-secretory defects, but tests to determine the cellular mechanisms underlying secretory abnormalities have not previously been reported. A patient with Sjogren's syndrome and distal renal tubular acidosis due to a secretory defect is described, whose kidney biopsy was examined by fluorescent immunocytochemistry with an antibody to the M(r) 31,000 subunit of the mammalian kidney vacuolar H(+)-ATPase and was compared with normal human kidney. Staining with the anti-H(+)-ATPase antibody in normal human kidney was detected in the brush border microvilli and subvillar invaginations of the proximal tubule and in intercalated cells in the collecting duct. A biopsy sample from the patient was devoid of any anti-H+-ATPase staining in the intercalated cells. Staining was also absent from the proximal tubule brush border microvilli but was present in the subvillar invaginations. Although autoantibodies to normal human kidney membrane proteins were detected in the serum by immunoblot analysis, no immunocytochemical evidence for anti-intercalated cell autoantibodies was observed in the patient's serum. This report demonstrates that the basis for the proton secretory defect in some patients with distal renal tubular acidosis is likely the absence of H(+)-ATPase in the intercalated cells. It also illustrates the potential diagnostic utility of anti-H(+)-ATPase antibodies in the classification of distal renal tubular acidoses.
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PMID:Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosis. 139 25

Membrane vesicles derived from the basolateral aspect of kidney proximal tubule cells are phosphorylated by ATP in the absence of Ca2+. This Mg(2+)-dependent, hydroxylamine-resistant phosphorylation was associated with a 50% inhibition of the (Ca(2+)+Mg2+)-ATPase activity measured upon addition of micromolar Ca2+ concentrations, enough to saturate the high-affinity sites of the Ca2+ pump. The presence of either the protein kinase inhibitor H7 or insulin during phosphorylation virtually eliminated the inhibitory effect associated with phosphorylation. However, insulin itself inhibited ATP hydrolysis by the (Ca(2+)+Mg2+)-ATPase when it was present in the assay medium containing buffer, ATP, Mg2+ and Ca2+, the hydrolytic activity being initiated by addition of the membranes without prior phosphorylation. These results suggest that insulin may play a role in regulating transepithelial Ca2+ transport in renal proximal tubules, and that its effects may be linked with a kinase-mediated process that depends on the functional state of the (Ca(2+)+Mg2+)-ATPase.
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PMID:Regulation of the (Ca(2+)+Mg2+)-ATPase of basolateral membranes from kidney proximal tubules by kinase-mediated phosphorylation and by insulin. 144 66

In addition to cyclooxygenase and lipoxygenase, arachidonic acid (AA) is metabolized by the cytochrome P-450 monooxygenase system. The kidney is one of the major extrahepatic tissues that display cytochrome P-450 enzyme activities, in particular the cortex, specifically the proximal tubule demonstrate the highest concentration. AA is metabolized by the renal cytochrome P-450 epoxygenase and omega/omega 1 hydroxylases to epoxyeicosatrienoic acids and omega/omega-1 alcohols (20- and 19-mono-hydroxyeicosatetraenoic acids), respectively. These metabolites possess a broad spectrum of biological and renal effects which include: vasodilation, vasoconstriction, inhibition and stimulation of Na(+)-K(+)-ATPase, inhibition of ion transport mechanisms, natriuresis, inhibition of renin release and stimulation of cell growth. These metabolites are endogenous constituents of the kidney and are present in urine with increasing concentration under pathological conditions such as pregnancy-induced hypertension. The cytochrome P-450-dependent metabolism of AA is specifically localized to the proximal tubule and exhibits developmental changes, i.e., renal production of metabolites is very low in the fetus, newborn and up to 3 weeks of age, after which a remarkable increase in enzyme activities is observed. These characteristics call attention to the importance of this enzyme system in producing cellular mediators for regulating renal function in normal and diseased states.
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PMID:The renal cytochrome P-450 arachidonic acid system. 145 35

A rat kidney- and intestine-specific cDNA (D2) that induces high-affinity, Na(+)-independent uptake of cystine and dibasic and neutral amino acids into cRNA-injected Xenopus oocytes was recently isolated by expression cloning in our laboratory (R. G. Wells and M. A. Hediger. Proc. Natl. Acad. Sci. USA 89: 5596-5600, 1992). At present it is not known whether the D2-encoded protein functions as a transporter or as a transporter activator. To gain more insight into the role of D2 in renal amino acid transport, we studied the site of its expression in the kidney. This was determined by Northern blot analysis and by using a combination of in situ hybridization and immunocytochemistry with antibodies that recognize specific proximal tubule segments. D2 antisense RNA hybridized to the same tubular segments that were strongly positive for anti-ecto-adenosinetriphosphatase but negative for carbonic anhydrase type IV and the facilitated glucose transporter GLUT2. We conclude that D2 mRNA is strongly expressed in the rat kidney proximal tubule S3 segment, although there is weak hybridization to the S1 and S2 segments. The signal is absent in all other parts of the kidney. The S3 specific expression of D2 mRNA coincides with the site of high-affinity transport of cystine and other amino acids, consistent with the proposed involvement of D2 in these processes.
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PMID:Expression of mRNA (D2) encoding a protein involved in amino acid transport in S3 proximal tubule. 148 85

HCO3-/CO2 can affect proximal tubule energy metabolism directly by serving as a substrate for metabolic reactions and indirectly through ATP utilization by HCO3(-)-coupled Na+ reabsorption and proton secretion. In this study, metabolic and transport roles of HCO3-/CO2 were examined by measuring the effects of HCO3-/CO2 removal and transport inhibitors on oxygen consumption (QO2) in suspensions of rabbit proximal tubules. Removal of medium HCO3-/CO2 inhibited ouabain-sensitive, ouabain-insensitive, and uncoupled QO2. Consistent with metabolic inhibition, the absence of HCO3-/CO2 also reduced tubule ATP content and stimulated lactate production. Analysis of the dependence of mitochondrial state 3 respiration on HCO3-/CO2 in digitonin-permeabilized tubules traced the metabolic inhibition to limitations in tricarboxylic acid cycle intermediate supply. Energy requirements for HCO3- transport were examined by measuring QO2 in response to acetazolamide, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), and the H(+)-adenosinetriphosphatase (H(+)-ATPase) inhibitor bafilomycin A. Acetazolamide had no effect on QO2, whereas DIDS-SITS and bafilomycin A reduced ouabain-insensitive QO2, consistent with inhibition of active proton secretion. DIDS-SITS did not affect ouabain-sensitive respiration, suggesting that HCO3(-)-dependent Na+ reabsorption may not be mediated through the Na(+)-K(+)-ATPase in this preparation.
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PMID:Relationship between HCO3- transport and oxidative metabolism in rabbit proximal tubule. 151 Jan 26


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