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)

We investigated the relation between atrial natriuretic factor (ANF) gene expression and the status of the renin-angiotensin system (RAS) in aortic tissue in rats made hypertensive by either aortic banding or by deoxycorticosterone acetate (DOCA)-salt administration. These experimental models of hypertension are known to have differences in terms of the status of RAS. ANF messenger RNA (mRNA) levels were measured in aortic tissue by using a newly developed quantitative competitive reverse transcription polymerase chain reaction (QC-RT-PCR) technique. Changes in the proportions of alpha1 and alpha2 isoforms of Na+K+-adenosine triphosphatase (ATPase) mRNA levels were used as indicators of aortic hypertrophy. Treatment with DOCA alone, salt alone, or DOCA-salt for 5 weeks increased aortic-weight/body-weight ratio and aortic angiotensinogen mRNA levels, but did not change alpha1 or alpha2 Na+K+-ATPase mRNA levels. Aortic ANF mRNA levels had a tendency to increase after treatment with DOCA, salt, or DOCA-salt, but this change did not reach statistical significance. Suprarenal aortic banding for 6 weeks or 12 weeks increased aortic-weight/body-weight ratio (12 weeks), decreased alpha2 Na+K+-ATPase and angiotensinogen mRNA levels, but did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Treatment with ramipril, an angiotensin-converting enzyme (ACE) inhibitor was carried out for 6 weeks just after aortic banding (prevention experiment) or after 6 weeks in rats that were banded for the previous 6 weeks (regression experiment). High-dose ramipril (1 mg/kg)--a treatment known to inhibit both tissue and circulating RAS--normalized aortic-weight/body-weight ratio, and also normalized alpha2 Na+K+-ATPase mRNA levels. Aortic angiotensinogen mRNA levels of banded rats treated with high-dose ramipril was higher than those of the normal control, sham operated, and banded rats. Treatment with high-dose ramipril did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Low-dose ramipril (10 microg/kg)--a treatment that selectively inhibits tissue RAS--normalized aortic-weight/body-weight ratio but did not normalize alpha2 Na+K+-ATPase mRNA levels (regression experiment) or angiotensinogen mRNA levels (prevention experiment) and did not change either alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. The results suggest that, in contrast to previous findings in heart and kidney, the regulation of ANF mRNA levels in aortic tissue is largely independent of pressure load, volume load, and plasma or tissue RAS. It is suggested that any antihypertrophic actions of ANF may be mediated by the increased circulating ANF levels and its interaction with its receptor or through CNP.
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PMID:Regulation of aortic atrial natriuretic factor and angiotensinogen in experimental hypertension. 986 8

Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied lung edema clearance in the isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with high VT (peak airway opening pressure [Pao] of approximately 35 cm H2O) and compared them with low VT ventilation (Pao approximately 8 cm H2O), moderate VT ventilation (Pao approximately 20 cm H2O), and nonventilated rats. Lung edema clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60 min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01), but did not change after low VT and moderate VT ventilation at any time point. Lung permeability to small (22Na+, [3H]mannitol) and large solutes (fluorescein isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Paralleling the impairment in lung edema clearance we found a decrease in Na,K-ATPase activity in alveolar type II (ATII) cells isolated from rats ventilated with moderate VT and high VT for 40 min without changes in alpha1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to clear edema by inhibiting active sodium transport and Na,K-ATPase function in the alveolar epithelium.
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PMID:Ventilator-associated lung injury decreases lung ability to clear edema in rats. 992 79

Hypothermic hyperkalemic circulatory arrest has been widely used for myocardial protection during heart surgery. Recent data showed that administration of triiodo-L-thyronine (T3) postoperatively enhanced ventricular function. The effect of hyperkalemic arrest in conjunction with thyroid hormone on the plasma membrane enzyme sodium/potassium-adenosine triphosphatase (Na/K-ATPase), was determined in cultured neonatal rat atrial and ventricular myocytes. Exposure of ventricular myocytes to hyperkalemic medium (50 mM KCl) in the absence of T3 increased expression of the Na/K-ATPase catalytic subunit mRNAs, alpha1 and alpha3 isoforms, by 1.9- and 1.5-fold, respectively (p<0.01), which were accompanied by similar increases (1.4- and 1.8-fold) in protein content. Addition of T3 to the hyperkalemic cultures attenuated these increases in Na/K-ATPase mRNA isoforms to levels of expression observed in cells treated with T3 (10(-8) M) alone. Similarly, expression of the alpha1 mRNA isoform in atrial myocytes was increased (p<0.05) by hyperkalemic conditions, and T3 treatment attenuated this effect. In contrast, although expression of the Na/K-ATPase beta1 mRNA in both atrial and ventricular myocytes was significantly increased by hyperkalemia, addition of T3 did not prevent the hyperkalemic response, and in atrial myocytes T3 significantly increased beta1 mRNA expression 1.8-fold. These results show that expression of cardiac Na/K-ATPase is regulated by T3 and hyperkalemia in an isoform and chamber specific manner, and suggest that use of hyperkalemic cardioplegia during heart surgery may alter plasma membrane ion function.
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PMID:Regulation of Na/K-ATPase gene expression by thyroid hormone and hyperkalemia in the heart. 1003 77

The effect of recombinant bovine IGF-I (rbIGF-I) on hypo-osmoregulatory ability and the effect of rbIGF-I and cortisol (F) alone and in combination on Na+,K+-ATPase expression in fresh water (FW) acclimated brown trout (Salmo trutta) were examined in two experiments. In Experiment 1, fish were given three injections of saline or 0.01 or 0.1 microgram rbIGF-I/g, respectively, and subjected to a 24-h 25 ppt seawater (SW) challenge test 24 h after the last injection. Fish treated with 0.01 and 0.1 microgram rbIGF-I/g had better hypo-osmoregulatory ability than control fish as judged by their higher level of muscle water content and lower plasma osmolality after 24 h exposure to 25 ppt SW. Compared with control fish, gill Na+,K+-ATPase activity was unchanged 24 h after the first injection at either dose but significantly stimulated after three injections of either dose of rbIGF-I. In Experiment 2, fish were given three injections of saline, 0.1 microgram rbIGF-I/g, 4 microgram F/g, or 0.1 microgram rbIGF-I + 4 microgram F/g and sampled in FW 24 h after the last injection. IGF-I and F had additive stimulatory effects on Na+,K+-ATPase activity and alpha-subunit Na+,K+-ATPase mRNA levels in the gill. Injections of IGF-I and F alone and in combination increased Na+,K+-ATPase-immunoreactive (NKIR) cell number in the primary gill filament but had no effect on secondary lamellar NKIR cell number. NKIR cells were abundant in kidney tubules, pyloric ceca, and posterior intestine, but Na+,K+-ATPase enzyme activity was unaffected by treatment with F and/or IGF-I in these tissues. F but not rbIGF-I increased in vitro fluid transport capacity in the posterior intestine. In addition to confirming an overall SW-adaptive effect of rbIGF-I and F in FW-acclimated S. trutta, the study suggests the effect to be associated with stimulation of chloride cell development and Na+,K+-ATPase expression in the gill. The study indicates that the stimulatory effects of the two hormones on Na+,K+-ATPase expression are additive, highly organ specific, and restricted to the primary filament epithelium of the gill.
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PMID:Effects of insulin-like growth factor-I and cortisol on Na+, K+-ATPase expression in osmoregulatory tissues of brown trout (Salmo trutta). 1006 95

The abundance of Na,K-ATPase and its alpha and beta subunit mRNAs is upregulated in cardiac and other target tissue by thyroid hormone (T3). Multiple Na,K-ATPase mRNA beta 1 species encoding an identical beta 1 polypeptide are expressed in the heart. The different mRNA beta 1 species result from utilization of two transcription start-sites in the first exon and multiple (five) poly(A) signals in the terminal exon of the beta 1 gene. In the present study we identify the mRNA beta 1 species that are expressed in rat ventricular myocardium under basal conditions, and determine whether they are differentially regulated by T3. mRNA beta 1 species were identified by 3'-RACE followed by DNA sequencing, and by Northern blotting using probes derived from different regions of rat cDNA beta 1. Five mRNA beta 1 species are expressed in rat heart: mRNA beta 1 species that are initiated at the first transcription start-site and end at the first, second and fifth poly(A) sites (resulting in mRNAs of 1630, 1810, and 2780 nucleotides), and mRNA beta 1 species initiated at the second transcription start-site and ending at the second and fifth poly(A) sites (resulting in mRNAs of 1500 and 2490 nucleotides); in order of increasing length, the five mRNAs constitute 0.04, 0.15, 0.38, 0.11 and 0.32 of total mRNA beta 1 content. In hypothyroid rats (induced by addition of propyl-thiouracil to the drinking water for 3 weeks), total mRNA beta 1 content decreased to 0.18 euthyroid levels, which was associated with a disproportionate 7.5-fold decrease in the abundance of the longest transcript (P < 0.05); transcripts initiating at the first transcription start-site and ending at the second poly(A) signal in hypothyroid hearts were 0.26 euthyroid levels (P < 0.05). Hyperthyroidism induced by injection of normal rats with three doses of 100 micrograms T3/100 g body weight every 48 h resulted in an overall approximately 2-fold increase in mRNA beta 1 content with no change in the fractional contribution of any of the mRNA beta 1 species. The results indicate a complex heterogeneity in the expression of mRNA beta 1 in myocardium.
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PMID:Na,K-ATPase mRNA beta 1 expression in rat myocardium--effect of thyroid status. 1009 77

Our original attempt was to examine whether inhibition of Na/H exchange in proximal tubule would affect the expression of basolateral membrane protein Na,K-ATPase. Three amiloride analogues were tested within the range of 10(-6) M to 10(-4) M in primary cultures of proximal tubule cells. Only ethylisopropyl amiloride (EIPA) dose-dependently downregulated Na,K-ATPase activity in cultured proximal tubule cells. The time course study revealed that EIPA (10(-4) M) significantly decreased Na,K-ATPase alpha- and alpha-mRNA abundance within 4 hr and suppressed Na,K-ATPase alpha- and beta-mRNA levels by 76.3 +/- 4.5% and 85.5 +/- 5.8%, respectively, within 24 hr. The decrease in Na,K-ATPase mRNA was followed by a decrease in Na,K-ATPase activity by 22.5 +/- 10.8% and 48.8 +/- 5.9% within 12 and 24 hr, respectively, which could be reflected by a coordinate decrease in levels of both alpha- and mature beta-protein. The cell viability was not affected until 20 hr of EIPA treatment, when an increase in LDH release and cell detachment was observed. Because EIPA rapidly decreased intracellular pH (pHi) to 6.7 within 2 hr and raising pHi to 6.6 by metabolic acidosis could not elicit changes in Na,K-ATPase activity, EIPA-induced downregulation of Na,K-ATPase should not be mediated through H+. In view of the time course of EIPA effects on Na,K-ATPase subunit mRNA, protein, activity and cell toxicity, the cytotoxic effect is likely resulted from a decrease in Na,K-ATPase activity. Take together, we conclude that EIPA induces downregulation of Na,K-ATPase expression via both pre- and post-translational mechanisms, which confers cytotoxic effects on proximal tubule cells.
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PMID:Ethyl isopropylamiloride downregulates Na,K-ATPase gene expression which confers cytotoxicity in primary proximal tubule cell cultures. 1009 66

The change of blood pressure and the induction of Na, K-ATPase alpha 1-subunit mRNA have been investigated in the renal cortex of aldosterone-treated hypertensive rat. The increase of blood pressure by aldosterone-treatment for 25 days was decreased by the treatment of amiloride or spironolactone. The level of Na, K-ATPase alpha 1-subunit mRNA of the renal cortex in aldosterone-treated rat was increased than that in the control, and its increase was repressed by treatment of spironolactone, but not altered by the treatment of amiloride. This result suggests that the increase of Na, K-ATPase alpha 1-subunit mRNA in the renal cortex of aldosterone-treated hypertensive rat may be related with the direct induction of Na, K-ATPase mRNA without the increase of Na-traffic through Na-channel.
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PMID:Aldosterone directly induces Na, K-ATPase alpha 1-subunit mRNA in the renal cortex of rat. 1020 70

The Na(+) pump, Na(+)-K(+)-ATPase, along with the Na(+) channel is essential for the removal of alveolar solute and fluid perinatally. Because Na(+)-pump mRNA and activity increase before birth and maternal glucocorticoids (GCs) influence Na(+)-K(+)-ATPase mRNA expression in fetal rat lung, we hypothesized that GCs increased Na(+)-K(+)-ATPase gene expression in a fetal lung epithelial cell line. After 24 h of exposure, dexamethasone increased the steady-state levels of Na(+)-K(+)-ATPase alpha(1) and beta(1) mRNA in a fetal rat lung epithelial cell line in a dose-dependent fashion (10(-7) to 10(-5) M). The maximal increase in mRNA levels was 3. 8-fold for alpha(1) and 2.8-fold for beta(1). The increase in mRNA was detected as early as 6 h for the beta(1)-subunit and 18 h for the alpha(1)-subunit, and both peaked at 24 h. This gene upregulation was not due to increased mRNA stability based on mRNA half-life determination after actinomycin D inhibition. Transfection experiments with alpha(1) and beta(1) promoter-reporter constructs demonstrated 3.2 +/- 0.5- and 2.6 +/- 0.4-fold increases, respectively, in promoter activity, consistent with transcriptional activation of the promoter-reporter construct. These findings, increased promoter activity with no change in stability, indicate that GCs increased Na(+)-K(+)-ATPase transcription in a fetal lung epithelial cell line.
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PMID:Na(+)-K(+)-ATPase gene regulation by glucocorticoids in a fetal lung epithelial cell line. 1040 48

Three-dimensional cardiac mapping in rabbits with nonischemic cardiomyopathy has shown that ventricular arrhythmias initiate by a nonreentrant mechanism that may be due to triggered activity from delayed afterdepolarizations. Delayed afterdepolarizations are thought to be due to spontaneous release of Ca(2+) from the sarcoplasmic reticulum (SR) and consequent activation of an inward Na(+)/Ca(2+) exchange (NaCaX) current. The goal of this study was to determine whether there is enhanced NaCaX gene expression and functional activity that may contribute to nonreentrant activation. Heart failure (HF) was induced in rabbits by combined aortic insufficiency and aortic constriction. HF rabbits had left ventricular enlargement (left ventricular end-diastolic dimension increased from 1.43+/-0.03 to 1.97+/-0.05 cm) and severely depressed function (fractional shortening reduced from 37% to 26%, P<0.02). Heart-to-body weight was increased by 79% in HF. Western blots showed a 93% increase in NaCaX protein in HF (P<0.04). NaCaX mRNA (7-kb transcript) was increased by 104% relative to the 18S rRNA in HF. A 14-kb NaCaX transcript was also seen in the HF rabbits, raising total NaCaX mRNA to 2.7-fold compared with controls. The amplitude of caffeine-induced contractures, used to assess SR Ca(2+) load, was not significantly different in HF. Relaxation and [Ca(2+)](i) decline during caffeine-induced contractures is attributable to Ca(2+) transport by NaCaX and was 61% and 45% faster in HF (P<0.05), respectively. NaCaX current measured under controlled voltage clamp conditions was also 2-fold higher in HF cells. SR Ca(2+)-ATPase mRNA and protein levels and Ca(2+) current density were not significantly altered in HF. Twitch amplitudes from HF myocytes were 26% smaller compared with control (P<0.02), but twitch relaxation and [Ca(2+)](i) decline (due largely to SR Ca(2+)-ATPase) were not altered. Thus myocytes and myocardium from HF rabbits exhibit enhanced NaCaX expression and function. The enhanced NaCaX activity may contribute to depressed contractions, increased transient inward current (for a given SR Ca(2+) release), delayed afterdepolarizations, and nonreentrant initiation of ventricular tachycardia in this arrhythmogenic model of HF.
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PMID:Upregulation of Na(+)/Ca(2+) exchanger expression and function in an arrhythmogenic rabbit model of heart failure. 1057 27

We examined vacuolar H+-ATPase (V-ATPase) structure, enzymatic properties, and protein and mRNA expression from mouse marrow cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1, 25(OH)2D3), which stimulates formation of bone-resorptive osteoclasts. V-ATPases from osteoclast-containing cultures were similar in ion and inhibitor sensitivities to the enzyme from kidney-derived sources. Immunopurified V-ATPase from 1,25(OH)2D3-stimulated cultures exhibited 20-fold greater ATPase activity than the enzyme from unstimulated cultures, which do not contain osteoclasts. In contrast, 1,25(OH)2D3-treated cultures contained only 2-fold more assembled V-ATPase, as determined by immunoprecipitation. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis similarly showed approximately 2-fold increases of V-ATPase mRNA and protein levels in 1,25(OH)2D3-treated cultures. The bulk of the relative difference in V-ATPase activity between the two cultures was due to a 10-fold difference in enzyme specific activity. Quantitative RT-PCR also revealed that expression levels of V-ATPase mRNAs reflected the stoichiometry of enzyme subunits in the assembled complex. These data indicate that in mouse bone marrow cultures, V-ATPase expression is controlled at the level of mRNA, and that increases in subunit expression and assembly cannot account for the 20-fold difference in enzyme activity in osteoclast-containing cultures. Therefore, osteoclast V-ATPase activity may be regulated by subtle alterations in enzyme structure or associated factors.
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PMID:Vacuolar H+-ATPase activity and expression in mouse bone marrow cultures. 1062 72


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