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: UNIPROT:P20020 (adenosine triphosphatase)
3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of culture conditions, serum supplementation or chemically defined medium and the influence of thyroid hormone were studied on the development of the Na+, K+-adenosine triphosphatase (Na+,K+-ATPase) and on the intracellular content of K+ and Na+ ions in cultures which either were greatly enriched in a neuronal cell type, the cerebellar granule cells, or contained a mixed population of cells (brain reaggregates). Foetal rat brain reaggregates displayed lower Na+,K+-ATPase activity when cultured in chemically defined medium than in the presence of serum. Supplementation of the serum-free medium with thyroid hormone resulted in a rise in the Na+,K+-ATPase activity and [3H]ouabain binding to levels similar to those found in the cultures grown in the serum-containing medium. Thyroid hormone had no significant effect on the Mg2+-ATPase activity and on the intracellular content of Na+ and K+ ions. In the granule cell-enriched cerebellar surface cultures the Na+,K+-ATPase activity was lower when the cells were grown in chemically defined medium compared with the serum-containing medium, and the intracellular Na+ to K+ ratio was higher. Thyroid hormone had no effect on the Na+,K+-ATPase activity, [3H]ouabain binding or Mg2+-ATPase activity. The hormone also failed to influence ATPase activities in cerebellar astrocytes maintained in chemically defined medium. Although thyroid hormone had no effect on the Na+,K+-ATPase activity of cultured cerebellar granule cells, treatment with the hormone resulted in a decrease in the ratio of intracellular Na+ to K+ ion content. The effect of the hormone on the Na+,K+-pump activity in live cells was therefore tested by estimating ouabain-sensitive 86Rb uptake. This was regulated as in other cell types, by the rate of Na+ entry: the Na+-ionophore monensin trebled the rate of 86Rb uptake, which was also increased (+30-100%) by 10% foetal calf serum, the maximal response being obtained by about 20 min exposure to serum. The effect was completely blocked by the Na+/H+ exchange inhibitor amiloride. The factor(s) in the serum responsible for the regulation of the Na+,K+-pump were, however, not the thyroid hormones, which failed to affect 86Rb uptake. On the basis of comparing thyroid hormone effects on the different cultures studied it was concluded that not every type of neural cell is target of the hormone action during development.
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PMID:Effect of thyroid hormone and serum on the development of Na+, K+-adenosine triphosphatase and associated ion fluxes in cultures from rat brain. 298 59

Thyroid hormone is known to modulate cell membrane sodium/potassium adenosine triphosphatase (Na/K-ATPase). To determine whether the activity of this enzyme differed in patients with nonthyroidal illness with low levels of circulating thyroid hormones and patients with documented clinical hypothyroidism, we measured Na/K-ATPase activity in red blood cells from patients with hypo- and hyperthyroidism, patients with nonthyroid disease with and without reduced circulating levels of thyroid hormone, and normal subjects. We also assessed whether the activity of this enzyme reflects decreased thyroid hormone action at the cellular level in patients with nonthyroidal illness. Hyperthyroidism was associated with decreased and hypothyroidism with increased erythrocyte Na/K-ATPase activity [142 +/- 24 (+/- SE) and 371 +/- 37 nmol Pi/mg X h; P less than 0.05 and P less than 0.01 compared to normal]. Enzyme activity in cells from patients with nonthyroidal illness and low levels of circulating T3 was significantly higher than that in cells from normal subjects (289 +/- 11 vs. 223 +/- 16 nmol Pi/mg X h; P less than 0.01), but was not significantly different from that in cells from hypothyroid patients. Red cell Na/K-ATPase activity in patients with nonthyroidal illness and normal thyroid function tests (185 +/- 38 nmol Pi/mg X h was indistinguishable from normal values. These data confirm that hyperthyroid patients have decreased red cell Na/K-ATPase activity and provide direct evidence that erythrocyte ATPase activity is increased in hypothyroid patients. The change in enzyme activity in patients with nonthyroidal illness and decreased circulating T3 levels was comparable to that in hypothyroidism. These results suggest that since red cell Na/K-ATPase activity does not distinguish between ill patients with low thyroid function tests and those with hypothyroidism, tissue hypothyroidism may exist in the former group of patients.
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PMID:Erythrocyte sodium/potassium adenosine triphosphatase in thyroid disease and nonthyroidal illness. 298 90

Na-K-adenosine triphosphatase (ATPase) activity was determined in individual nephron segments obtained from the kidneys of euthyroid and hypothyroid rats. One group of animals was made hypothyroid by feeding 0.05% aminotriazole (ATZ) in the diet for 2 weeks. A second group received the same amount of ATZ plus 500 micrograms/kg body weight of L-thyroxine (T4) given subcutaneously each day for 2 weeks. A third group received the same diet without ATZ or T4. There was a 57% (P less than 0.01) decrease in Na-K-ATPase activity in the proximal convoluted tubule (PCT) in ATZ-treated rats that was corrected by the simultaneous administration of T4 with ATZ. A smaller (15% to 25%) and statistically nonsignificant decrease in Na-K-ATPase activity was observed in the cortical portion of the proximal straight tubule and in both the cortical and the medullary portions of the thick ascending limb in ATZ-treated rats. These changes in the enzyme activity were also corrected by simultaneous administration of T4 with ATZ. The results suggest that under the conditions of these experiments the PCT is a major site of action of thyroid hormone in the rat kidney.
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PMID:Effects of thyroid hormone on Na-K-adenosine triphosphatase activity along the rat nephron. 299 54

The relationship between net tubular reabsorption of sodium and renal microsomal sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186+/-14 vs. 246+/-12 mueq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4+/-2.4 vs. 65.8+/-2.3 mumol inorganic phosphate (P(t))/mg protein per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5'-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 10(-12) to 10(-5) M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intact controls. Despite persistence of the hypothyroid state, Na-K-ATPase specific activity also increased to levels not significantly different from euthyroid animals. These data suggest that decreased tubular sodium transport is a major determinant of the reduction in renal Na-K-ATPase in thyroid deficiency since the latter can be reversed by increasing sodium reabsorption during continuing hypothyroidism. Furthermore, the modest sodium leak of hypothyroid animals does not appear to be due to decreased Na-K-ATPase since it was not corrected by uninephrectomy despite restoration of both cortical and medullary Na-K-ATPase activity to normal by this maneuver. The close correlation between net sodium reabsorption and Na-K-ATPase in all the experimental situations described here demonstrates that renal Na-K-ATPase changes adaptively in hyper- or hypothyroidism as it does in numerous situations in the normal animal, in accord with its postulated role in the active transport of sodium across the renal tubule.
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PMID:Renal sodium- and potassium-activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. 434 43

Kinetic analyses of the Na+-K+-adenosine triphosphatase (ATPase) system were performed in brain and heart preparations from young mature (4 mo old) and healthy aged (25 mo old) rats. The K+-activated p-nitrophenylphosphatase (K+-pNPPase) method was used to assess activity of the enzyme system. Ouabain inhibition of K+-pNPPase activity was also examined. A significant age-related decrease in maximal velocity (Vmax) was found in cardiac K+-pNPPase activity, but no changes were seen in the K+ concentration for half-maximal velocity (K0.5). No age differences in Vmax or K0.5 were seen for brain. No differences in ouabain inhibition were found in either brain or heart. In a second experiment, the major component of the age-related decline in cardiac K+-pNPPase activity was found to occur between 5 and 14 mo of age, a period during which plasma thyroxine had previously been found to decline in the same animals. Since peripheral Na+-K+-ATPase activity is partly thyroid hormone dependent, the age-dependent decrease in cardiac enzyme activity appears to be secondary to neuroendocrine changes.
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PMID:Kinetic studies of the Na+-K+-ATPase enzyme system in brain and heart of aging rats. 609 4

The effects of thyroid hormone treatment on brown adipose tissue (BAT) and liver metabolism were assessed by measuring oxygen consumption, sodium-potassium adenosine triphosphatase (Na-K-ATPase), and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities in tissues from triiodothyronine- (T3) and vehicle-injected (for 3 days) newborn and adult rabbits. In the newborns, basal BAT cellular respiration was increased [mean (%/- SE) = 119 +/- 18 vs. 65 +/- 4 microliter O2/10(6) cells-1 . h in controls (P less than 0.005)], whereas hepatic respiration was unchanged. Ouabain had no effect on basal BAT cellular respiration, but suppressed hepatic respiration by 30% in both newborn groups. T3 treatment had no effect on NE- (10(-6) M) stimulated BAT respiration, whereas adult hepatic respiration was increased almost twofold. alpha-GPD activities were increased in both newborn BAT and adult liver but not in newborn liver. Na-K-ATPase activity was significantly increased only in newborn liver. In conclusion, 1) both BAT and liver are thyroid-hormone sensitive in the newborn rabbit, but the responses to T3 treatment are different in the two tissues; 2) the failure to stimulate both hepatic alpha-GPD and respiration in the newborn appears to be a developmental phenomenon characteristic of the rabbit; 3) thyroid hormones have little effect on sodium transport-dependent respiration in either BAT of liver in the newborn rabbit.
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PMID:Thyroid hormone-sensitive brown adipose tissue respiration in the newborn rabbit. 627 13

Surgical thyroidectomy decreased (Na+ + K+)-dependent adenosine triphosphatase (Na-K-ATPase) activity in rat submandibular glands. Three successive doses of triiodothyronine (100 microgram/100 g of body wt) to euthyroid and hypothyroid rats produced 24 and 23 per cent increase in the enzyme activity, compared to control values. When hypothyroid rats were given smaller doses of triiodothyronine (4 microgram/100 g body wt every 48 h) for 27 days, Na-K-ATPase activity increased 40 per cent over the corresponding values in the control hypothyroid rats. Thus, thyroid hormone acts on rat submandibular glands to increase the Na-K-ATPase activity of that target tissue.
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PMID:Influence of thyroid hormone on (Na+ + K+)-dependent adenosine triphosphatase activity in rat submandibular glands. 628 Jun 56

The cardiac activity of a series of analogues of the positive inotropic bipyridines amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) and milrinone (2-methyl-5-cyano-[3,4'-bipyridin]-6(1H)-one) was evaluated in vitro in a rabbit myocardial membrane Mg(2+)-dependent, Ca(2+)-stimulable adenosine triphosphatase (Ca(2+)-ATPase) model and structure-activity relationships were compared for nine closely related derivatives. In the present studies, a 5-bromo analogue of milrinone stimulated myocardial membrane Ca(2+)-ATPase significantly (10(-7) M; P < 0.001 vs control, with 67% of the activity of milrinone), whereas a 2'-methyl-2H-milrinone derivative was inactive. Although amrinone was inactive in this assay, its 2-methyl analogue was stimulatory. However, analogues lacking a 2-substituent (with or without a 5-cyano group) or with the 3-N position blocked by a methyl group did not stimulate myocardial membrane Ca(2+)-ATPase activity. Structural data for these bipyridines show that those with either a 2- or 2'-methyl substituent have a twist conformation, whereas those without are nearly planar. Activity data reveal that those bipyridines with a nonplanar conformation are more active in the Ca(2+)-ATPase assay. Further study of milrinone analogues with a 2'-methyl substituent shows that even though the effect on the twist angle is equivalent to that of 2-methyl substitution, these analogues are less potent. Data for this series reveal that the prerequisites for Ca(2+)-ATPase stimulation include not only a 2-methyl to maintain a twist conformation but also a free 3-N position and a 5-substituent. This model for optimal activity in the myocardial membrane Ca(2+)-ATPase system differs from those proposed for phosphodiesterase enzyme receptor recognition only in the requirement for a nonplanar molecule. We have previously shown that milrinone, but not amrinone, shares structural homology with thyroxine and was able to stimulate myocardial membrane Ca(2+)-ATPase activity in a manner similar to the thyroid hormone. Additionally, milrinone, but not amrinone, was an effective competitor for thyroxine binding to the serum transport protein transthyretin. Analysis of the milrinone-transthyretin crystal complex confirms the structural homology between milrinone and thyroid hormone which is not shared by amrinone. Modeling studies of the binding interactions of milrinone analogues indicate that the 2-desmethylmilrinone analogue, the most inhibitory analogue, lacks the hydrophobic contacts present in milrinone in its transthyretin-bound complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structure-activity relationships of milrinone analogues determined in vitro in a rabbit heart membrane Ca(2+)-ATPase model. 778 30

The effects of thyroid hormone (T3) treatment on liver Na,K-adenosine triphosphatase (Na,K-ATPase) at the levels of subunit messenger RNA (mRNA), enzymatic activity, and enzyme content were studied in euthyroid rats injected for 5 consecutive days with T3. Northern and slot blot analyses of polyadenylated mRNA revealed that T3 treatment coordinately increases the level of mRNA encoding the alpha 1- and beta 1-subunits, approximately 4- and 3-fold, respectively, above basal levels. To determine whether this increase in the subunit mRNA consequently results in an increase in the synthesis of the enzyme, a modified liver cell fractionation procedure was developed, and the subcellular fractions from control and T3-treated livers were examined biochemically. Western blot analysis and Na,K-ATPase assay demonstrated that T3 treatment resulted in a 2-fold increase in both the amount and activity of the enzyme. Furthermore, the Western blot analysis of endoglycosidase-H-treated membrane fractions revealed an increase in the amount of the precursor beta-subunit in the T3-treated liver rough microsomal fraction, suggesting that an increase in subunit synthesis contributes at least partially to the increase in the rat liver Na,K-ATPase by T3 treatment.
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PMID:The effect of thyroid hormone treatment on the gene expression and enzyme activity of rat liver sodium-potassium dependent adenosine triphosphatase. 783 97

Thyroid hormone (T3) increases the transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) gene (SERCA 2) through three thyroid hormone response elements. The existence of repetitive cis elements with different configurations is likely to serve specific functions such as interactions with nuclear transcription factors. In addition, the presence of different T3 receptor isoforms (T3Rs) may contribute to another level of complexity in providing specificity for T3 action. In this study, we investigated T3R alpha 1-vs. T3R beta 1-specific interactions with the myocyte enhancer-specific factor-2 (MEF-2) on the expression of the SERCA 2 gene in transient transfection assays in embryonal heart-derived H9c2 cells. MEF-2a in combination with either T3R alpha 1 or T3R beta 1 isoforms resulted in a 2.5-fold increase in SERCA 2 transgene expression in the absence of T3. Addition of T3 did not induce any further increase in SERCA 2 expression when T3R alpha 1 and MEF-2a expression vectors were cotransfected. In contrast, in the presence of T3R beta 1 and MEF-2, the addition of T3 increased chlorampenicol acetyltransferase activity by an additional 2.2-fold to a total 5.5-fold increase. The interaction between MEF-2a and T3R is transcription factor specific because another factor that binds to MEF-2 consensus sites (heart factor 1b) was not able to interact with T3R. In addition, MEF-2a failed to interact with other nuclear factors (cAMP response element-binding protein and Egr-1) that stimulate SERCA 2 gene transcription. In addition, we found that a single homologous thyroid hormone response element is not able to mediate the interactions between MEF-2a and T3Rs to increase SERCA 2 gene transcription. Our findings point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.
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PMID:Transcription of the rat sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene is increased by 3,5,3'-triiodothyronine receptor isoform-specific interactions with the myocyte-specific enhancer factor-2a. 897 81


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