Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na,K-ATPase molecules containing the alpha 1, alpha 2*, and alpha 3* isoforms expressed in HeLa cells exhibit a two- to threefold difference in their K0.5 for Na+ (alpha 1 = alpha 2* < alpha 3*). To investigate the structural basis for this difference, chimeric alpha 1/alpha 3* isoform cDNAs were constructed and expressed in HeLa cells. Na,K-ATPase containing each alpha isoform chimera was analyzed for its Na+ dependence properties. Results of these experiments do not reveal a region in the alpha 1 or alpha 3* isoform that is clearly responsible for the apparent affinity for Na+. It is possible that molecular interactions involving amino acids that span virtually the entire Na,K-ATPase molecule contribute to the determination of this parameter.
 ...
PMID:Chimeric rat Na,K-ATPase alpha 1/alpha 3* isoforms. Analysis of the structural basis for differences in Na+ requirements in the alpha 1 and alpha 3* isoforms. 128 13

The Na+,K(+)-ATPase alpha 3 isoform has recently been demonstrated immunochemically in human brain. Conclusive biochemical evidence, however, is still lacking. In this study, a unique 50-kDa polypeptide, which is known to be specific to the rat alpha 3 isoform, has been found in human brainstem Na+,K(+)-ATPase following formic acid treatment of the purified alpha isoform proteins. Human alpha 3 Na+,K(+)-ATPase is also highly sensitive to ouabain inhibition, with a 50% ouabain inhibition value of 1.0 x 10(-7) M. These results provide clear and direct evidence for the existence of the alpha 3 isoform in human brain.
 ...
PMID:Highly ouabain-sensitive alpha 3 isoform of Na+,K(+)-ATPase in human brain. 131 Jul 23

To investigate the functional role of the different Na+, K(+)-ATPase alpha (catalytic) subunit isoforms in neuronal cells, we used quantitative in situ hybridization with riboprobes specific for alpha 1, alpha 2, and alpha 3 isoforms to measure the level of alpha isoform-specific expression in the neuroendocrine cells of the supraoptic (SON) and paraventricular (PVN) nuclei of rat hypothalamus. A prolonged increase in electrical activity of these cells, achieved by 5 days of salt treatment, increased the amount of alpha 1 isoform mRNA in the SON and PVN by 50%. Levels of alpha 1 mRNA in other brain regions and levels of alpha 2 and alpha 3 mRNAs were not affected by salt treatment. We conclude that the alpha 1 isoform Na+, K(+)-ATPase may be specifically adapted to pump out Na+, which enters the cells through voltage-gated channels during neuronal depolarization.
 ...
PMID:Activity-dependent regulation of Na+, K(+)-ATPase alpha isoform mRNA expression in vivo. 132 Dec 32

Regulation of Na,K-ATPase mRNA alpha isoform and mRNA beta expression by thyroid hormone (T3) in neonatal rat myocardium was examined. In euthyroid neonates between ages of 2 and 5 days, mRNA alpha 1, mRNA alpha 3, and mRNA beta 1 abundances were nearly constant while mRNA alpha 2 was undetectable. During the interval between postnatal days 5 and 15, mRNA alpha 3 decreased to negligible levels and mRNA alpha 2 became expressed and increased in abundance to account for approximately 20% of the mRNA alpha pool by the 15th postnatal day. To examine the effect of T3 on this developmental program, neonates were injected with 75 micrograms T3/100 g body weight or diluent alone on the second and third postnatal days and myocardial Na,K-ATPase subunit-mRNA abundances were determined on the third and fourth postnatal days. Because T3 treatment increased the RNA/DNA ratios of myocardial tissue, the subunit-mRNA abundances were normalized per unit DNA. Following 24 and 48 hr of T3 treatment, the abundances of mRNA alpha 1, mRNA alpha 3, and mRNA beta 1 increased, while mRNA alpha 2 continued to remain undetectable during the 2-day interval between the second to fourth postnatal days. It is concluded that T3 augments the abundance of Na,K-ATPase subunit mRNAs that are already being expressed in the neonatal rat myocardium. The results further suggest that T3 does not act as a "molecular switch" in the developmental expression of the mRNA alpha isoforms in rat myocardium during the first four postnatal days.
 ...
PMID:Thyroid hormone regulation of Na,K-ATPase subunit-mRNA expression in neonatal rat myocardium. 164 35

Clones of cDNA that code for an isoform of the Artemia franciscana Na/K ATPase alpha subunit (NaKA alpha) have been isolated. The sequence of the longest of these clones (pArATNa136) is 3595 nucleotides; it codes for a 1004-amino acid protein whose sequence is identical to that of two previously sequenced Artemia NaKA alpha peptides. The encoded protein is over 73% identical to Drosophila melanogaster and vertebrate NaKA alpha s, and 73.8% identical to another Artemia NaKA alpha isoform previously described (named alpha 2850 in this article). The two Artemia cDNA clones code for mRNAs of different size; the clone pArATNa136 codes for a 4.5-kb mRNA while the alpha 2850 clone codes for a 3.6-kb mRNA. The degree of homology and the different size of the mRNAs encoded by both cDNAs suggest that they code for two different isoforms of the protein.
 ...
PMID:Cloning of a cDNA encoding an Artemia franciscana Na/K ATPase alpha-subunit. 165 19

The Na,K-ATPase alpha isoform (alpha 1, alpha 2, and alpha 3) and beta subunit genes exhibit a complex pattern of expression during heart development. To identify possible molecular signals that regulate the differential expression of these genes, isolated neonatal rat myocardial and non-myocardial cells were cultured in chemically defined medium and the responses of the multiple Na,K-ATPase subunit mRNAs to various hormones were tested. Myocardiocytes in control cultures express primarily alpha 1 and beta mRNAs. Triiodothyronine (T3) induced the expression of alpha 2, alpha 3, and beta mRNAs without influencing alpha 1 mRNA levels. Dexamethasone (DEX) treatment similarly induced alpha 2 mRNA levels, but the abundance of the other subunit transcripts remained unaltered. T3 and DEX together caused increases in alpha 2 and beta mRNA, increments similar to that observed with T3 alone. However, DEX specifically repressed the induction of alpha 3 mRNA by T3. Both hormones stimulated corresponding changes in the sarcolemma concentration of these Na,K-ATPase isozymes. Addition of norepinephrine to the cultures had little appreciable effect on expression of the alpha isoform and beta mRNAs. Although characterized less extensively, control cultures of non-myocardiocytes expressed alpha 1, alpha 3, and beta mRNAs, of which only the beta mRNA was stimulated by T3. These data indicate that thyroid and glucocorticoid hormones differentially regulate the expression of multiple alpha isoform and beta subunit mRNAs of Na,K-ATPase in cardiocytes in vitro and, therefore, may also be important physiological modulators in vivo.
 ...
PMID:Thyroid and glucocorticoid hormones regulate the expression of multiple Na,K-ATPase genes in cultured neonatal rat cardiac myocytes. 168 3

1. mRNA transcripts for three isoforms of the alpha subunit of (Na,K)-ATPase have been previously identified in the rat nervous system and designated alpha 1, alpha 2 and alpha 3. 2. In order to study the localization and expression of the different alpha isoform mRNAs on a regional and cellular level in the brain, we prepared probes from the unique 3' untranslated region of rat alpha 1 cDNA and from a segment containing a portion of the translated region of rat alpha 3 cDNA. These probes were used in dot blot and in situ hybridization assays of rat brain. 3. alpha 1 mRNA was found predominantly in cerebral cortex, dentate gyrus of hippocampus, and specific isolated brain-stem nuclei such as locus ceruleus and motor nuclei V and VII. In contrast alpha 3 mRNA was found predominantly in pyramidal neurons in the deep layers of cerebral cortex, in both pyramidal and dentate gyrus neurons of the hippocampus, and in neurons of most subcortical structures of the thalamus, basal ganglia, and brain-stem nuclei. 4. In the cerebellum, Purkinje cells showed predominantly alpha 3, as did stellate and basket cells. The granule cells contained predominantly alpha 1. 5. These experiments show that mRNAs for both alpha 1 and alpha 3 isoforms of (Na,K)-ATPase are found in neurons of the CNS. The isoforms have unique cellular and regional distributions, which in some cases overlap.
 ...
PMID:Differential distribution of (Na, K)-ATPase alpha isoforms in the central nervous system. 185 65

In photoreceptors, Na+, K(+)-ATPase maintains the ion gradients which power the dark current that sustains the response to light. The enzyme is composed of at least two polypeptides: alpha (the catalytic subunit) and beta. Three different isoforms of the alpha subunit and two isoforms of the beta subunit have been identified in rat. In some tissues, the isoenzymes have been shown to be differentially expressed during development or in response to varying physiological conditions. RNAs prepared from isolated photoreceptors and from whole retina were analyzed on blots that were hybridized with cDNA probes for the alpha 1, alpha 2, alpha 3, beta 1 and beta 2 isoforms. The predominant alpha and beta subunit mRNAs present in the photoreceptor preparation were those encoding the alpha 3 and beta 2 isoforms, accounting for 85% of the total alpha signal and 79% of the total beta signal, respectively. Proportions of each mRNA were similar in retina, but very different from those observed in two control tissues, brain and kidney. To confirm that the alpha-subunit mRNA species detected were translated, membranes prepared from isolated photoreceptors and whole retina were examined by immunoblotting. The antibodies detected a pattern of alpha isoform distribution in these tissues and in kidney and brain controls that agreed remarkably well with the pattern of mRNA expression in the same tissues. Moreover, the alpha 3 isoform was detectable in the inner segment plasma membrane of the photoreceptor by electron microscopic immunocytochemistry. These results indicate that alpha 3, and beta 2 are the predominant isoforms of Na+, K(+)-ATPase expressed in photoreceptors and retina.
 ...
PMID:Na+, K(+)-ATPase of the photoreceptor: selective expression of alpha 3 and beta 2 isoforms. 217 74

Sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na+,K+-ATPase alpha-subunit messenger RNA isoforms (alpha 2 and alpha 3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another alpha isoform (alpha 1) and of beta-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.
 ...
PMID:Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension. 283 7

The developmental expression of the multiple isozymes of Na,K-ATPase in rat brain, heart, lung, kidney, and skeletal muscle from fetal (14 days gestation) to adult (55 days) was investigated at the molecular level with cDNA probes specific for the multiple catalytic alpha isoform (alpha 1, alpha 2, alpha 3) and beta subunit mRNAs. Northern and RNA slot blot analyses revealed that these mRNAs are regulated in a tissue-specific manner. The multiple alpha isoform and beta subunit mRNAs appear to be regulated coordinately during ontogenesis with maximum expression occurring between 15 and 25 days of age for brain, heart, kidney, and skeletal muscle, whereas peak expression in lung was observed between 2 and 4 days of neonatal life. Brain tissue showed between 10- and 17-fold increases in the levels of expression for the three individual alpha isoform mRNAs. The alpha 3 mRNA was found to be the predominant alpha isoform transcript in fetal as well as adult brain. Examination of heart tissue showed alpha 1 mRNA to be the major catalytic subunit during development. However, a developmentally regulated transition in alpha 2 and alpha 3 mRNA expression was observed in heart between 7 and 14 days after birth. The alpha 3 mRNA was expressed primarily in fetal and neonatal heart tissue, while alpha 2 mRNA was expressed in juvenile and adult tissue. In kidney and lung, alpha 1 mRNA was the predominant alpha isoform transcript showing temporary increases in expression of 2- and 4-fold, respectively, during development. In contrast to the other tissues, muscle expressed predominantly alpha 2 mRNA following birth, the levels increasing approximately 89-fold during myogenesis. Thus, each tissue examined exhibits a distinct pattern of expression for the Na,K-ATPase catalytic alpha isoforms during ontogenesis.
 ...
PMID:Tissue-specific and developmental regulation of rat Na,K-ATPase catalytic alpha isoform and beta subunit mRNAs. 283 91


1 2 3 4 5 6 Next >>