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)

The green sturgeon is a long-lived, highly migratory species with populations that are currently listed as threatened. Their anadromous life history requires that they make osmo- and ionoregulatory adjustments in order to maintain a consistent internal milieu as they move between fresh-, brackish-, and seawater. We acclimated juvenile green sturgeon (121 +/- 10.0 g) to 0 (freshwater; FW), 15 (estuarine; EST), and 24 g/l (SF Bay water; BAY) at 18 degrees C for 2 weeks and measured the physiological and biochemical responses with respect to osmo- and ionoregulatory mechanisms. Plasma osmolality in EST- and BAY-acclimated sturgeon was elevated relative to FW-acclimated sturgeon (P < 0.01), but there was no difference in muscle water content or abundance of stress proteins. Branchial Na(+), K(+)-ATPase (NKA) activity was also unchanged, but abundance within mitochondrion-rich cells (MRC) was greater in BAY-acclimated sturgeon (P < 0.01). FW-acclimated sturgeon had the greatest NKA abundance when assessed at the level of the entire tissue (P < 0.01), but there were no differences in v-type H(+)ATPase (VHA) activity or abundance between salinities. The Na(+), K(+), 2Cl(-) co-transporter (NKCC) was present in FW-acclimated sturgeon gills, but the overall abundance was lower relative to sturgeon in EST or BAY water (P < 0.01) where this enzyme is crucial to hypoosmoregulation. Branchial caspase 3/7 activity was significantly affected by acclimation salinity (P < 0.05) where the overall trend was for activity to increase with salinity as has been commonly observed in teleosts. Sturgeon of this age/size class were able to survive and acclimate following a salinity transfer with minimal signs of osmotic stress. The presence of the NKCC in FW-acclimated sturgeon may indicate the development of SW-readiness at this age/size.
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PMID:Osmo- and ionoregulatory responses of green sturgeon (Acipenser medirostris) to salinity acclimation. 1906 9

The time-course of programmed cell death (apoptosis) during reorganization of gill epithelium in salinity-stressed tilapia was analyzed using a recently developed method based on laser scanning cytometry (LSC) of dissociated gill cells. Apoptosis in mitochondria-rich cells (MRC) was distinguished from that in other cell types using Na(+)/K(+) ATPase (NKA) as a cell-specific marker. Caspase 3/7 activity in MRC, assessed using LSC and microplate assays, increased significantly starting at 6 h of salinity stress and remained elevated for at least 5 days. This time-course of apoptosis in MRC during acute salinity stress was reflected in elevated apoptotic DNA fragmentation. In parallel to induction of apoptosis, MRC showed a pronounced shift to G2 phase of the cell cycle, which is indicative of G2/M cell cycle arrest, and an increase in NKA abundance per MRC. Unlike in MRC, apoptosis was not significantly increased in other gill cell types, although there was a small transient increase in DNA fragmentation at 6 h. G2 arrest was also observed. Overall, we interpret our data as evidence for a significant role of apoptosis in the extensive reorganization of MRC populations that takes place during salinity acclimation, perhaps similar to its well-established role during organismal development.
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PMID:Prolonged apoptosis in mitochondria-rich cells of tilapia (Oreochromis mossambicus) exposed to elevated salinity. 1913 43

Intracellular Na(+) concentration ([Na(+)](i)) is very important in modulating the contractile and electrical activity of the heart. Upon electrical excitation of the myocardium, voltage-dependent Na(+) channels open, triggering the upstroke of the action potential (AP). During the AP, Ca(2+) enters the myocytes via L-type Ca(2+) channels. This triggers Ca(2+) release from the sarcoplasmic reticulum (SR) and thus activates contraction. Relaxation occurs when cytosolic Ca(2+) declines, mainly due to re-uptake into the SR via SR Ca(2+)-ATPase and extrusion from the cell via the Na(+)/Ca(2+) exchanger (NCX). NCX extrudes one Ca(2+) ion in exchange for three Na(+) ions and its activity is critically regulated by [Na(+)](i). Thus, via NCX, [Na(+)](i) is centrally involved in the regulation of intracellular [Ca(2+)] and contractility. Na(+) brought in by Na(+) channels, NCX and other Na(+) entry pathways is extruded by the Na(+)/K(+) pump (NKA) to keep [Na(+)](i) low. NKA is regulated by phospholemman, a small sarcolemmal protein that associates with NKA. Unphosphorylated phospholemman inhibits NKA by decreasing the pump affinity for internal Na(+) and this inhibition is relieved upon phosphorylation. Here we discuss the main characteristics of the Na(+) transport pathways in cardiac myocytes and their physiological and pathophysiological relevance.
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PMID:Na+ transport in cardiac myocytes; Implications for excitation-contraction coupling. 1924 7

The goal of our study was to evaluate the origin of the increased O(2) consumption in electrically stimulated left ventricular slices of isoproterenol-induced hypertrophied rat hearts with normal left ventricular pressure. O(2) consumption per minute (mVO(2)) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO(2), i.e., mVO(2) without electrical stimulation, was significantly smaller, but mVO(2) for the total Ca(2+) handling in excitation-contraction coupling (E-C coupling mVO(2)), i.e., delta mVO(2) (=mVO(2) with stimulation - mVO(2) without stimulation), was significantly larger in the hypertrophied heart. Furthermore, the fraction of E-C coupling mVO(2) was markedly altered in the hypertrophied heart. Namely, mVO(2) consumed by sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was depressed by 40%; mVO(2) consumed by the Na(+)/K(+)-ATPase (NKA)-Na(+)/Ca(2+) exchange (NCX) coupling was increased by 100%. The depressed mVO(2) consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser(16) phospholamban and SERCA2. The increase in NKA-NCX coupling mVO(2) was supported by marked augmentation of NCX current. However, the increase in NCX current was not due to the increase in NCX1 protein expression, but was attributable to attenuation of the intrinsic inactivation mechanisms. The present results demonstrated that the altered origin of the increased E-C coupling mVO(2) in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca(2+)) and increased NCX activity coupled to NKA activity (1ATP: Ca(2+)). Taken together, we conclude that the energetically less efficient Ca(2+) extrusion pathway evenly contributes to Ca(2+) handling in E-C coupling in the present hypertrophy model.
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PMID:Increased O2 consumption in excitation-contraction coupling in hypertrophied rat heart slices related to increased Na+ -Ca2+ exchange activity. 1934 May 63

Cardiac Na(+)-K(+)-ATPase (NKA) regulates intracellular Na(+), which in turn affects intracellular Ca(2+) and contractility via the Na(+)/Ca(2+) exchanger. Extracellular K(+) concentration ([K(+)]) is a central regulator of NKA activity. Phospholemman (PLM) has recently been recognized as a critical regulator of NKA in the heart. PLM reduces the intracellular Na(+) affinity of NKA, an effect relieved by PLM phosphorylation. Here we tested whether the NKA alpha(1)- vs. alpha(2)- isoforms have different external K(+) sensitivity and whether PLM and PKA activation affects the NKA affinity for K(+) in mouse cardiac myocytes. We measured the external [K(+)] dependence of the pump current generated by the ouabain-resistant NKA isoform in myocytes from wild-type (WT) mice (i.e., current due to NKA-alpha(1)) and mice in which the NKA isoforms have swapped ouabain affinities (alpha(1) is ouabain sensitive and alpha(2) is ouabain resistant) to assess current due to NKA-alpha(2). We found that NKA-alpha(1) has a higher affinity for external K(+) than NKA-alpha(2) [half-maximal pump activation (K(0.5)) = 1.5 +/- 0.1 vs. 2.9 +/- 0.3 mM]. The apparent external K(+) affinity of NKA was significantly lower in myocytes from WT vs. PLM-knockout mice (K(0.5) = 2.0 +/- 0.2 vs. 1.05 +/- 0.08 mM). However, PKA activation by isoproterenol (1 microM) did not alter the K(0.5) of NKA for external K(+) in WT myocytes. We conclude that 1) NKA-alpha(1) has higher affinity for K(+) than NKA-alpha(2) in cardiac myocytes, 2) PLM decreases the apparent external K(+) affinity of NKA, and 3) phosphorylation of PLM at the cytosolic domain does not alter apparent extracellular K(+) affinity of NKA.
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PMID:Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman. 1957 Aug 95

Maitotoxin (MTX) activates Ca(2+)-permeable nonselective cation channels and causes a dramatic increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in every cell examined to date, but the molecular identity of the channels involved remains unknown. A clue came from studies of a structurally related marine toxin called palytoxin (PTX). PTX binds to the plasmalemmal Na(+)-K(+)-ATPase (NKA) and converts the Na(+) pump into a nonselective cation channel. Given the high permeability of the MTX channel for Ca(2+), we considered the possibility that MTX may bind to the plasmalemmal Ca(2+)-ATPase (PMCA) pump, and like PTX, convert the pump into a channel. To test this hypothesis, the PMCA was overexpressed in Spodoptera frugiperda (Sf9) insect cells and in human embryonic kidneys (HEK) 293 cells. In both cell types, enhanced expression of the PMCA was associated with a significant increase in MTX-induced whole cell membrane currents. The effect of MTX on whole cell currents in both wild-type and PMCA overexpressing HEK cells was sensitive to pump ligands including Ca(2+) and ATP. MTX-induced currents were significantly reduced by knockdown of PMCA1 in HEK cells using small interfering RNA or in mouse embryonic fibroblasts from genetically modified mice with the PMCA1(+/-) PMCA4(-/-) genotype. Finally, PMCA catalytic activity (i.e., Ca(2+)-ATPase) in isolated membranes, or in purified PMCA preparations, was inhibited by MTX. Together, these results suggest that MTX binds to and converts the PMCA pump into a Ca(2+)-permeable nonselective cation channel.
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PMID:Maitotoxin converts the plasmalemmal Ca(2+) pump into a Ca(2+)-permeable nonselective cation channel. 1979 42

In fishes, variation in paracellular permeability is important for regulating salt and water balance. Paracellular permeability is maintained by TJs in vertebrate epithelia. This study examined the spatial distribution and effects of salinity on claudin-3 isoform mRNA expression and abundance along the gastrointestinal (GI) tract of the euryhaline puffer fish (Tetraodon nigroviridis) and related these to morphological heterogeneity of the TJ complex. The puffer fish GI tract was divided into three regions (anterior, middle and posterior) and four isoforms of claudin-3 (Tncldn3a, Tncldn3b, Tncldn3c and Tncldn3d) were found to be expressed in each section. The effect of freshwater (FW) or seawater (SW) acclimation on regional 1) Tncldn3 isoform mRNA abundance, 2) TJ complex morphology and 3) Na(+)-K(+)-ATPase (NKA) activity was examined. In situ hybridization indicated that all Tncldn3 isoforms localized to the mucosal epithelium in the intestine. The mRNA abundance of Tncldn3 isoforms varied spatially along the GI tract. Furthermore, region as well as isoform specific alterations in mRNA abundance could be observed along the GI tract in response to salinity change. Qualitative TEM observations suggested that the depth of TJ complexes increased from anterior to posterior along the GI tract and that TJ complexes in the GI tract of FW fish were deeper than those in SW. NKA activity increased from anterior to posterior in fish acclimated to FW, whereas activity in fish acclimated to SW was uniformly high along the length of the intestine. Taken together data; (1) suggest a progressive decrease in epithelial permeability from anterior to posterior along the longitudinal axis of the puffer fish GI tract, (2) indicate that claudin-3 protein isoforms may play a role in regulating paracellular movement of solutes across this epithelium, and (3) provide further evidence that claudin-3 proteins are involved in the homeostatic control of salt and water balance in fishes.
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PMID:Spatial and salinity-induced alterations in claudin-3 isoform mRNA along the gastrointestinal tract of the pufferfish Tetraodon nigroviridis. 1989 30

This is the first direct physiological evidence in support of the ionoregulatory hypothesis, challenging the long-held assumption that teleost gills develop initially for gas exchange. Resting unidirectional sodium (Na(+)) uptake and oxygen (O(2)) uptake across the skin and gills were measured simultaneously in larval rainbow trout, Oncorhynchus mykiss, during development. In soft and hard water, Na(+) uptake shifted to the gills by 15 and 16 days post-hatch (dph) while O(2) uptake took 50-80% longer and shifted by 23 and 28 dph, respectively. This suggests that gills are required for ionoregulation prior to gas exchange in developing rainbow trout. The age of transition for Na(+) uptake, gill Na(+), K(+)-ATPase (NKA) alpha-subunit protein expression and gill NKA enzyme activity were not significantly different between soft and hard water-reared groups, which suggests a lack of plasticity in gill ionoregulatory development. In rainbow trout, the gills assume a dominant role in ionoregulation before gas exchange, suggesting that ionoregulation may be the initial driving force for gill development. Further investigation is required to determine whether this pattern is consistent with other teleosts and more basal fishes during early development to gain insight into the role of ionoregulation in vertebrate gill evolution.
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PMID:Ions first: Na+ uptake shifts from the skin to the gills before O2 uptake in developing rainbow trout, Oncorhynchus mykiss. 2007 86

Na(+), K(+)-ATPase (NKA) is involved, through its role as a major driving force for electrochemical gradients, in a range of transmembrane transport processes. Maintenance of homeostasis in anadromous salmonids requires modulation of several gill ion secretory proteins as part of the preparatory adaptation and acclimation to marine life. Atlantic salmon smolts were exposed to combinations of low pH and inorganic aluminum (acid/Al(i)) in freshwater (FW) and were then transferred to seawater (SW) for studies of post-smolt performance. Gill mRNA levels of four NKA-alpha isoforms (alpha1a, alpha1b, alpha1c and alpha3) of the catalytic NKA subunit and NKA enzyme activity were measured. Moderate acid/Al treatment (MOD, pH 5.9+/-0.3, 15+/-9microgl(-1)Al(i)) prevented the FW preparatory increase in NKA activity observed in control (CON, pH 6.9+/-0.1, 8+/-3microgl(-1)Al(i)) smolts, while high acid/Al treatment (SEV, pH 5.6+/-0.2, 30+/-7microgl(-1)Al(i)) caused a rapid and persistent reduction in NKA activity. Correspondingly, a 3.3-fold increase in plasma glucose levels in the SEV groups concurrent with a decrease in plasma chloride levels suggest that acid/Al exposed fish were stressed and experienced problems maintaining ion homeostasis. Gill NKA activities in acid/Al exposed groups were re-established after 28 days in SW. Both long (9 days) and short-term (2.5 days) treatments had significant impact on isoform-specific Na(+), K(+)-ATPase alpha-subunit mRNA abundance in the FW period. Acid/Al exposed groups lacked the preparatory increases in all NKA-alpha isoform mRNA levels seen in the CON group, except for alpha1a. In contrast to the other isoforms measured, alpha1a mRNA abundance decreased sharply upon SW transfer, supporting the hypothesis of isozyme shifting as a mechanism of altering the gill from an ion absorbing to an ion excreting tissue during smoltification and SW exposure. Adult return rates to the Imsa river were significantly reduced both in short-term (78% of controls) and long-term (55% of controls) acid/Al exposures, emphasising the physiological and ecological consequences of acid/Al exposure during smoltification.
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PMID:Effects of acidic water and aluminum exposure on gill Na(+), K(+)-ATPase alpha-subunit isoforms, enzyme activity, physiology and return rates in Atlantic salmon (Salmo salar L.). 2007 44

Ouabain is both a cardiac glycoside used in therapy of congestive heart failure and an endogenous steroid hormone. It specifically binds to Na(+), K(+)-ATPase (NKA) and blocks its activity. Overdose of ouabain induces retinal damage. In different species ouabain-induced retinal degeneration affects different cell types. In fish and rabbit ouabain induces retinal cell death preferentially in the ganglion cell layer and outer photoreceptor segments respectively. In rats, the pattern of NKA expression has been studied with most detail among retinal neurons. In addition, ouabain selectively destroyed some types of neurons in rodents. However, ouabain-sensitive retinal neurons remain unclear in rats. We show here that injection of ouabain into the rat vitreous body induced dramatic cell death in the inner nuclear layer (INL). The cell death was time- and dose-dependent. Ouabain-induced dying cells in the INL were TUNEL-positive. Immunohistochemistry analysis revealed that there was a significant decrease in the number of calbindin D-28K- and syntaxin-1-positive horizontal and amacrine cells in the INL of ouabain-treated rat retinas. Thus our results revealed that the horizontal and amacrine cells are the most sensitive cell types to ouabain in the retina of Sprague-Dawley rat.
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PMID:The new targets of ouabain in retinal interneurons of Sprague-Dawley rats. 2010 55


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