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)

This work, using RT PCR, studied expression of mRNAs encoding ion transporters, the Na/H antiporter (NHE1), the beta subunit of the Na,K-ATPase pump (ATP1B1), the NaK2Cl symporter (NKCC1), and some proteins unrelated to ion transport: the serum and glucocorticoid dependent kinase (hSGK), beta-actin, a glycolytic enzyme (GAPDH), and regulators of proliferation and apoptosis (p53, Bcl-2) during activation of human lymphocytes with phytohemagglutinin for 4-24 h. Within 24 hours the mRNA levels of NHE1, beta-actin, Bcl-2, and p53 increased by more than 100%, the mRNA levels of ATP1B1, GAPDH, and hSGK, by about 50%, while the mRNA levels of NKCC1 decreased transiently. These results indicate a differential transcriptional control of NHE1, ATP1B1, and NKCC1 following a proliferative stimulus of human lymphocytes.
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PMID:Differential transcription of ion transporters, NHE1, ATP1B1, NKCC1 in human peripheral blood lymphocytes activated to proliferation. 1127 79

The presence and cellular distribution of key H+ and HCO3- transport proteins was studied in human salivary ducts. Immunofluorescence and immunoperoxidase light microscopy was applied, using specific antibodies against the NHE1 and NHE3 isoforms of the Na+/H+ exchanger, against the 31 and 70 kDa subunits of the vacuolar H+-ATPase and against the electrogenic Na+-HCO3- cotransporter. The results show basolateral NHE1 and apical NHE3 in human submandibular, parotid and sublingual duct cells. Vacuolar H+-ATPase was found predominantly in the apical membrane of parotid, submandibular and sublingual duct cells, although it was absent in certain parotid striated duct cells. The Na+-HCO3- cotransporter was predominantly expressed in the apical membrane of parotid and sublingual striated ducts, and intracellularly distributed in the distal parts of the gland tree and in submandibular ducts. The results indicate that HCO3- transport properties of salivary ducts may vary not only between gland and species, but even in different duct segments of the same gland as well.
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PMID:H+ and HCO3- transporters in human salivary ducts. An immunohistochemical study. 1175 10

Regulation of intracellular pH (pHi) was studied in isolated rat renal inner medullary thin limbs of Henle's loop in bicarbonate/phosphate-buffered medium with high pCO2, high osmolality ( congruent with670 mosmol/kg H2O; 270 mM urea; 180 mM NaCl), organic osmolytes, and a pH of 6.8 to approximate the physiological in vivo environment. The pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pHi. Resting pHi was always acid and significantly more acid in descending thin limb (DTL) cells than in ascending thin limb (ATL) cells from pure or mixed-type thin limbs. Resting pHi was slightly but significantly higher in both DTLs and ATLs in high osmolality ( approximately 670 mosmol/kg H2O) than in low osmolality ( approximately 290 mosmol/kg H2O) medium but not when sucrose replaced urea. In both DTLs and ATLs the rate of recovery of pHi following additional acidification with an NH4Cl pulse was reduced by Na+ removal from the medium and by the addition of 60 microM HOE642 (an inhibitor of the Na+/H+ exchanger, NHE1), 55 microM S1611 (inhibitor of Na+/H+ exchanger, NHE3), 1 microM bafilomycin A1 (an inhibitor of vacuolar H+ -ATPase), or 20 microM Schering 28080 (an inhibitor of H+ -K+ -ATPase) to the medium. Resting pHi was also reduced by 60 microM HOE642, 55 microM S1611, and 20 microM Schering 28080. In both DTLs and ATLs, RT-PCR revealed message for NHE1, NHE3, and vacuolar H+ -ATPase; immunocytochemistry demonstrated the expression of the protein for NHE1 (basolateral membrane), NHE3 (luminal membrane), and H+ -K+ -ATPase (luminal membrane). These data suggest that pHi in rat inner medullary thin limbs is regulated by urea and by basolateral and luminal H+ extrusion via NHE1, NHE3, vacuolar H+ -ATPase, and H+ -K+ -ATPase.
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PMID:Regulation of intracellular pH in rat renal inner medullary thin limbs of Henle's loop. 1181 Feb 16

The Na,K-ATPase generates electrochemical gradients that are used to drive the coupled transport of many ions and nutrients across the plasma membrane. The functional enzyme is comprised of an alpha and beta subunit and families of isoforms for both subunits exist. Recent studies in this laboratory have identified a biological role for the Na,K-ATPase alpha4 isoform in sperm motility. Here we further investigate the role of the Na,K-ATPase carrying the alpha4 isoform, showing again that ouabain eliminates sperm motility, and in addition, that nigericin, a H+/K+ ionophore, and monensin, a H+/Na+ ionophore, reinitiate motility. These data, along with the observation that the K+ ionophore valinomycin has no effect on the motility of ouabain-inhibited sperm, suggest that ouabain may change intracellular H+ levels in a manner that is incompatible with sperm motility. We have also localized NHE1 and NHE5, known regulators of intracellular H+ content, to the same region of the sperm as the Na,K-ATPase alpha4 isoform. These data highlight the important role of the Na,K-ATPase alpha4 isoform in regulating intracellular H(+) levels, and provide evidence suggesting the involvement of the Na+/H+ exchanger, which is critical for maintaining normal sperm motility.
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PMID:Roles of the Na,K-ATPase alpha4 isoform and the Na+/H+ exchanger in sperm motility. 1211 99

After massive small bowel resection (MSBR), the remnant small intestine adapts to restore Na absorptive function. The possibility that this occurs through increases in cellular Na absorptive capacity was examined by assessing the regional effects of 50% proximal MSBR on the function and expression of the apical membrane Na/H exchangers (NHEs) NHE2 and NHE3. Morphometric analysis confirmed adaptive changes consistent with villus hypertrophy, particularly distal to the anastomosis. Villus epithelium prepared by light mucosal scrapings from 2-wk-postresected and -posttransected control rats exhibited comparable brush-border hydrolase activities, total cell protein per DNA, and villin expression but increased basolateral Na-K-ATPase activity. Parallel increases of two- to threefold in protein and mRNA abundance of NHE2 and NHE3 were observed only in ileal regions distal to the anastomosis of resected rats. Basolateral NHE1 expression was unchanged. After 80% resection, increases in NHE2 and NHE3 became evident in proximal colon. We conclude that increased enterocyte expression and function of apical membrane NHEs in regions distal to the anastomosis play a role in the adaptive process after MSBR. The increased luminal Na load to distal bowel regions after proximal resection may stimulate increases in apical membrane NHE gene transcription and protein expression.
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PMID:Region-specific adaptation of apical Na/H exchangers after extensive proximal small bowel resection. 1222 58

Elevated Na(+)/H(+) exchanger activity and intracellular acidosis have previously been demonstrated in white blood cells isolated from women who have suffered from a pre-eclamptic pregnancy. The mechanisms underlying this abnormality and the implications in pre-eclamptic pregnancies are, at present, unclear. In this study, we used neutrophils from third trimester pre-eclamptic patients and third trimester normotensive pregnant controls to determine Na(+)/H(+) exchanger isoform-1 (NHE-1) activity and intracellular pH. This was performed using a well-validated technique involving flurometry and a pH sensitive dye, 2,7'Bis-(carboxyethyl) 5.6 carboxyfluorescein acetomethyl ester (BCECF-AM). Time course experiments were performed to assess the contribution of plasma factors to intracellular pH measurements. Plasma digoxin-like factor (DLF) was assessed in both patients and normotensive controls. Neutrophil intracellular pH was significantly lower in the pre-eclamptic patients (7.15 +/- 0.050) compared with the normotensive pregnant controls (7.36 +/- 0.027; P<.001). NHE-1 activity (in mmol/L/min) was significantly higher in the pre-eclamptics (32.4 +/- 1.9) compared with the normotensive neutrophils (27.1 +/- 1.6; P =.038). Times course experiments showed that mean pre-eclamptic intracellular pH increased from 7.11 +/- 0.049 to 7.25 +/- 0.043 after 2 hours of incubation. DLF, measured as amount of inorganic phosphate liberated from adenosine triphosphate (ATP), was significantly lower when plasma from the pre-eclamptic patients was incubated with the enzyme compared with plasma from the normotensive pregnant women (54.9 +/- 2.6 nmol/mL plasma v 63.91 +/- 1.7 nmol/mL plasma, n = 6, P =.018 unpaired Student's t test). The results suggest that elevated NHE-1 activity and intracellular acidosis are intermediate phenotypes in women who have pre-eclampsia. Intracellular pH may have been affected by plasma as shown in the time course experiments. DLF, an inhibitor of Na(+)/K(+)ATPase, may contribute to this intracellular acidosis in pre-eclamptic neutrophils.
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PMID:Neutrophil intracellular pH and Na+/H+ exchanger activity in pre-eclampsia. 1252 67

The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na(+)/H(+)) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes.
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PMID:The relationship between Na(+)/H(+) exchanger expression and tyrosinase activity in human melanocytes. 1526 99

The current models for branchial acid excretion in fishes include Na(+)/H(+) exchange and the electrogenic excretion of H+ via H+-ATPase. The predominant route of acid excretion in some freshwater fishes is thought to be via the H+-ATPase/Na+ channel system. The euryhaline Fundulus heteroclitus may not fit this profile even when adapted to freshwater (FW). We hypothesize that the Na+/H+ exchanger (NHE) in this species may play a predominant role in acid-base regulation for both marine and FW adapted animals. Acidosis induced by ambient hypercapnia (1% CO2 in air), resulted in an increase in net H+ excretion to the water in F. heteroclitus pre-adapted to FW, brackish (isoosmotic; BW) and seawater (SW). Both FW and SW adapted mummichogs were tested for NHE protein expression using mammalian NHE antibodies, and we identified NHE-like immunoreactive proteins in gill membrane preparations from both groups. Hypercapnia induced a approximately three-fold elevation in gill NHE2-like protein in FW animals but SW adapted fish showed inconsistent NHE3-like protein expression. There was no change in NHE-1 levels in FW fish. In contrast, SW animals demonstrated a significant increase in both NHE1 and NHE3-like proteins following hypercapnia but limited expression of the NHE2 protein. We hypothesize that different isoforms of NHE may be preferentially expressed depending on the salinity to which the animals are adapted. Net H+ transfers during acidosis may be driven, at least in part by the action of these transporters.
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PMID:The effect of environmental hypercapnia and salinity on the expression of NHE-like isoforms in the gills of a euryhaline fish (Fundulus heteroclitus). 1588 Jul 78

The choroid plexus epithelium secretes electrolytes and fluid in the brain ventricular lumen at high rates. Several channels and ion carriers have been identified as likely mediators of this transport in rodent choroid plexus. This study aimed to map several of these proteins to the human choroid plexus. Immunoperoxidase-histochemistry was employed to determine the cellular and subcellular localization of the proteins. The water channel, aquaporin (AQP) 1, was predominantly situated in the apical plasma membrane domain, although distinct basolateral and endothelial immunoreactivity was also observed. The Na(+)-K(+)-ATPase alpha(1)-subunit was exclusively localized apically in the human choroid plexus epithelial cells. Immunoreactivity for the Na(+)-K(+)-2Cl(-) cotransporter, NKCC1, was likewise confined to the apical plasma membrane domain of the epithelium. The Cl(-)/HCO(3)(-) exchanger, AE2, was localized basolaterally, as was the Na(+)-dependent Cl(-)/HCO(3)(-) exchanger, NCBE, and the electroneutral Na(+)-HCO(3)(-) cotransporter, NBCn1. No immunoreactivity was found toward the Na(+)-dependent acid/base transporters NHE1 or NBCe2. Hence, the human choroid plexus epithelium displays an almost identical distribution pattern of water channels and Na(+) transporters as the rat and mouse choroid plexus. This general cross species pattern suggests central roles for these transporters in choroid plexus functions such as cerebrospinal fluid production.
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PMID:Distribution of sodium transporters and aquaporin-1 in the human choroid plexus. 1648 71

We studied the proton secretion mechanisms involved with pHi regulation in immortalized rat proximal tubule cells (IRPTC), a SV40-immortalized cell line derived from rat proximal tubule, and characterized the effects of serum deprivation on them. Using pHi measurements with the fluorescent probe BCECF, we demonstrated that the IRPTC express both Na+/H+ exchanger and H+-ATPase, but only NHE1 is modulated by serum deprivation. In these cells, 24 h of serum starvation increased pHi from 7.08+/-0.008 (n=34) to 7.18+/-0.018 (n=33) as well as the pH recovery rate from intracellular acidification with NH4Cl from 0.29+/-0.022 pH U/min (n=14) to 0.50+/-0.024 pH U/min (n=14), without modifying their buffering capacity. These effects were followed by several modifications in morphological features, indicating an increase in differentiation status. The altered activity of NHE1 was consistent with an increase of both transcription and translation of the antiporter, as the utilization of actinomycin D and cycloheximide significantly inhibited the upregulation of NHE1 induced by serum withdrawal. Inhibition of tyrosine phosphorylation by genistein blocked the serum deprivation-dependent activation of NHE. Moreover, the pharmacological inhibition of MEK1/2, the upstream activator of ERK1/2 by UO-126, significantly inhibited the stimulatory effect of serum starvation on Na+/H+ exchanger activity, whereas the putative p38 MAPK inhibitor SB-203580 failed to cause any effect on pHi recovery rates. Our findings indicate that during IRPTC differentiation by serum deprivation, there was a net enhancement of NHE1 activity. This upregulation of NHE by serum removal was consistent with an increase of RNA and protein synthesis of the exchanger, which depends on tyrosine kinase phosphorylation and ERK pathway activation.
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PMID:Increased NHE1 expression is associated with serum deprivation-induced differentiation in immortalized rat proximal tubule cells. 1649 13


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