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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we demonstrate the stimulation of both glutamate uptake and Na,K-ATPase activity in rat astrocyte cultures in response to a sublethal ischemic insult in vitro. To measure sodium pump activity and glutamate uptake, 3H-glutamate and 86Rb were simultaneously added to the cultures in the presence or absence of 2 mM ouabain. Na,K-ATPase activity was defined as ouabain-sensitive 86Rb uptake. Cell death was assessed by exclusion of the vital dye, calcein-AM from cells. Concomitant transient increases (2-3 fold above control levels) in both Na,K-ATPase and glutamate transporter activities were observed in astrocytes after 2-4 hours of ischemia. By contrast, 24 hours of ischemia caused a profound loss of both activities which paralleled significant cell death. The addition of 5 mM glucose to the cells after 4 hours of ischemia prevented the loss of sodium pump activity and glutamate uptake, and rescued astrocytes from the lethal effects of 24 hours of ischemia.
...
PMID:Glutamate uptake and Na,K-ATPase activity in rat astrocyte cultures exposed to ischemia. 941 61

The release of excitatory amino acids from Schwann cell cultures in the rat was monitored using high-performance liquid chromatography. The basal concentration of glutamate and aspartate was 33 +/- 4 nM (mean +/- S.E.M., n = 12) and 8 +/- 1 nM (mean +/- S.E.M., n = 12), respectively. ATP (100 microM) caused a receptor-mediated increase in release of glutamate and aspartate from Schwann cell cultures. Bath application of adenosine (100 microM) was without effect on release of excitatory amino acids suggesting involvement of P2 receptors. Suramin, a competitive antagonist at P2 receptors, prevented the response to ATP. The release of excitatory amino acids evoked by ATP was not abolished in calcium-depleted saline. Pretreatment of the Schwann cultures with 50 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetracetic acid-acetoxymethyl ester (BAPTA-AM) abolished the effect of ATP. ATP-evoked release of glutamate from cultured Schwann cells was significantly reduced by thapsigargin (1 microM), an inhibitor of Ca(2+)-ATPase of the Ca2+ pump of internal stores. U73122, a selective inhibitor of receptor-coupled phospholipase C-dependent processes, abolished stimulatory effect of ATP suggesting that ATP's action is mediated through an inositol 1,4,5-triphosphate-sensitive calcium store. The action of ATP was not blocked by L-trans-pyrrolidine-2,4-dicarboxylate, an inhibitor of the electrogenic glutamate transporter, nor was it blocked in Na(+)-free medium, and glutamate release was not stimulated by a depolarizing stimulus, suggesting that ATP-evoked release of glutamate from Schwann cells is not due to the reversal of the glutamate uptake. An anion transport blocker, furosemide, reduced ATP-induced glutamate release. These results suggest that ATP-stimulated glutamate and aspartate release from Schwann cells may be through a calcium-dependent furosemide-sensitive mechanism.
...
PMID:ATP stimulates release of excitatory amino acids from cultured Schwann cells. 948 46

1. Reactive oxygen species (ROS) can be generated in biological tissues, including the retina, in particular under or after ischemia. They can provoke cell necrosis by reacting with cell components or they can trigger programmed cell death by activating specific targets. 2. Experiments based on electroretinography and electron spin resonance spin trapping analysis show that ROS are produced in the rabbit retina during ischemic episodes themselves as well as reperfusion. ROS are also generated as a consequence of ischemia by overstimulation of glutamate ionotropic receptors and calcium-dependent activation of enzymes such as phospholipase A2 and nitric oxide synthase. 3. The targets of ROS that can be responsible for functional damage of the retina are numerous: Na+-K+-ATPase inhibition leads to ionic imbalance and electroretinogram alteration; inhibition of glutamate transporter contributes to excitotoxicity. In addition, ROS can be deleterious by inducing protein synthesis (e.g., apoptotic proteins, vascular endothelial growth factor/vascular permeability factor). 4. In this short review, we consider the various mechanisms of ROS generation in retinal ischemia and the different effects of ROS so as to suggest possible effects of neuroprotective agents.
...
PMID:Free radicals in retinal ischemia. 951 74

Glutamate plays an important metabolic role in virtually every vertebrate cell. In particular, glutamate is the most common excitatory neurotransmitter in the vertebrate central nervous system. As such, the mechanism by which glutamate is diverted from its normal metabolic activities toward its role as a neurotransmitter has, in recent years, been systematically investigated. In glutamatergic nerve endings, synaptic vesicles accumulate and store a proportion of the cellular glutamate pool and, in response to appropriate signals, release glutamate into the synaptic cleft by exocytosis. Glutamate accumulation is accomplished by virtue of a glutamate uptake system present in the synaptic vesicle membrane. The uptake system consists of a transport protein, remarkably specific for glutamate, and a vacuolar-type H+-ATPase, which provides the coupling between ATP hydrolysis and glutamate transport. The precise manner in which the glutamate transporter and H+-ATPase operate is currently the subject of debate. Recent data relevant to this debate are reviewed in this article. Additionally, pharmacological agents thought to specifically interact with the vesicular glutamate transporter are discussed. Finally, a newly discovered, endogenous inhibitor of vesicular uptake, inhibitory protein factor (IPF), is discussed with some speculations as to its potential role as a presynaptic modulator of neurotransmission.
...
PMID:Glutamate transport and storage in synaptic vesicles. 963 55

A strain of Bacillus designated TA2.A1, isolated from a thermal spring in Te Aroha, New Zealand, grew optimally at pH 9.2 and 70 degrees C. Bacillus strain TA2.A1 utilized glutamate as a sole carbon and energy source for growth, and sodium chloride (>5 mM) was an obligate requirement for growth. Growth on glutamate was inhibited by monensin and amiloride, both inhibitors that collapse the sodium gradient (DeltapNa) across the cell membrane. N, N-Dicyclohexylcarbodiimide inhibited the growth of Bacillus strain TA2.A1, suggesting that an F1F0-ATPase (H type) was being used to generate cellular ATP needed for anabolic reactions. Vanadate, an inhibitor of V-type ATPases, did not affect the growth of Bacillus strain TA2.A1. Glutamate transport by Bacillus strain TA2.A1 could be driven by an artificial membrane potential (DeltaPsi), but only when sodium was present. In the absence of sodium, the rate of DeltaPsi-driven glutamate uptake was fourfold lower. No glutamate transport was observed in the presence of DeltapNa alone (i.e., no DeltaPsi). Glutamate uptake was specifically inhibited by monensin, and the Km for sodium was 5.6 mM. The Hill plot had a slope of approximately 1, suggesting that sodium binding was noncooperative and that the glutamate transporter had a single binding site for sodium. Glutamate transport was not affected by the protonophore carbonyl cyanide m-chlorophenylhydrazone, suggesting that the transmembrane pH gradient was not required for glutamate transport. The rate of glutamate transport increased with increasing glutamate concentration; the Km for glutamate was 2.90 microM, and the Vmax was 0.7 nmol. min-1 mg of protein. Glutamate transport was specifically inhibited by glutamate analogues.
...
PMID:Sodium-dependent glutamate uptake by an alkaliphilic, thermophilic Bacillus strain, TA2.A1. 1032 19

We characterized swelling of rat cultured astrocytes induced by L-glutamate and its analogues. Among L-glutamate receptor agonists, L-glutamate, L-aspartate, L-cysteic acid, DL-homocysteic acid, quisqualate and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) increased astrocytic intracellular volume (3H-OMG space), while kainate, and N-methyl-D-aspartate did not. Threo-beta-hydroxyaspartate (TBHA), D-aspartate and L-trans-pyrrolidine-2,4-dicarboxylic acid, high-affinity substrates for Na+-dependent L-glutamate transporters, increased astrocytic 3H-OMG space. L-Glutamate (0.5 mM) increased astrocytic 3H-OMG space to 300% of control in 40-60 min. The increase in 3H-OMG space by 1 mM TBHA was comparable to the L-glutamate-induced one. After a 10 min-exposure to 0.5 mM L-glutamate, astrocytic 3H-OMG space was further increased to 200% even in the absence of L-glutamate. Astrocytes transiently exposed to L-glutamate did not increase their cell volume in K+-free medium and in the presence of 1 mM ouabain, a Na+-K+ ATPase inhibitor. The increase after a transient exposure was also observed by a treatment of 1 mM TBHA, but not by 0.5 mM quisqualate. These results suggest that the volume increases after a transient treatment are mediated by activation of Na+-dependent L-glutamate transporter.
...
PMID:Transient treatments with L-glutamate and threo-beta-hydroxyaspartate induce swelling of rat cultured astrocytes. 1067 81

The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.
...
PMID:A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics. 1106 79

The results presented support the view that the modulation of Na(+),K(+)-ATPase activity in living cells involves the association/dissociation of acetylated tubulin with the enzyme. We found that the stimulation of Na(+),K(+)-ATPase activity by L-glutamate correlates with decreased acetylated tubulin quantity associated with the enzyme. The effect of L-glutamate was abolished by the glutamate transporter inhibitor DL-threo-beta-hydroxyaspartate but was not affected by either specific agonists or antagonists. The effect of L-glutamate seems to be mediated by Na(+) entry resulting from glutamate transport, since the Na(+) ionophore monensin produced stimulation of Na(+),K(+)-ATPase activity with concomitant decrease of acetylated tubulin quantity associated with the enzyme.
...
PMID:Involvement of acetylated tubulin in the regulation of Na+,K+ -ATPase activity in cultured astrocytes. 1252 71

The SLC32 family comprises a single member: the vesicular inhibitory amino acid transporter (VIAAT) or vesicular GABA transporter (VGAT). It belongs to a eukaryotic-specific superfamily of H(+)-coupled amino acid transporters, which also comprises the mammalian SLC36 and SLC38 transporters. VIAAT exchanges GABA or glycine for protons. It is present on synaptic vesicles of GABAergic and glycinergic neurons, and in some endocrine cells, where it ensures the H(+)-ATPase-driven uptake, and subsequent exocytotic release, of inhibitory amino acids. Despite a similar function in vesicular neurotransmitter loading, VIAAT is not related to the vesicular glutamate transporter (VGLUT, SLC17) or the vesicular monoamine transporter/vesicular acetylcholine transporter (VMAT/VACHT, SLC18) proteins.
...
PMID:The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids. 1275 Aug 92

Transgenic mice targeted for the c-ros gene, which are fertile when heterozygous (HET), but infertile when homozygous (knockout, KO) and associated with failure in pubertal differentiation of the epididymal initial segment, provide a model for studying the role of the epididymal luminal environment in sperm development. Luminal fluid from the cauda epididymidis was measured by both ion-selective microelectrodes and pH strips to be 0.3 pH units higher in the KO than HET. Of the genes responsible for luminal acidification, expression of mRNA of vacuolar H(+)-ATPase was found in all epididymal regions, but with no difference between KO and HET. Immunohistochemistry showed its presence in epithelial apical cells and clear cells. The Na(+)-hydrogen exchanger NHE2 was expressed at mRNA and protein levels in the caput but only marginally detectable if at all in the distal epididymis. This was compensated for by NHE3 which was expressed strongest in the cauda region, in agreement with immunohistochemical staining. Quantification of Western blot data revealed slight, but significant, decreases of NHE2 in the caput and of NHE3 in the cauda in the KO mice. The increase in luminal fluid pH in the KO mice could also be contributed to by other epithelial regulating factors including the Na(+)-dependent glutamate transporter EAAC1 formerly reported to be down regulated in the KO.
...
PMID:Increased luminal pH in the epididymis of infertile c-ros knockout mice and the expression of sodium-hydrogen exchangers and vacuolar proton pump H+-ATPase. 1509 36


<< Previous 1 2 3 4 5 Next >>

---