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)

Several classes of anti-inflammatory agents including acetyl-salicylic acid, salicylic acid, flufenamic acid, phenyl-butazone, indometacin, oxyphenyl-butazone, and mefenamic acid were found to be inhibitors of rat liver mitochondrial ATPase in both intact and freeze-ruptured mitochondria. The freeze-ruptured mitochondrial ATPase was found to be Mg2+- and ATP-concentration dependent. The standard uncoupler, 2,4-dinitrophenol, not possessing anti-inflammatory activity, activates the enzyme in both preparations. A number of compounds of various structural classes possessing no anti-inflammatory property in vivo were found to have no inhibitory effect on the enzyme. This inhibition of ATPase by anti-inflammatory agents could be used as an in vitro test method for the primary screening of potential anti-inflammatory agents.
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PMID:Influence of anti-inflammatory agents on rat liver mitochondrial ATPase. 13 89

Many drugs or chemicals had markedly different effects on the cytotoxicity induced by Pseudomonas aeruginosa exotoxin A (PE) or Corynebacterium diphtheriae exotoxin (DE). The glycolytic inhibitor NaF protected cells from DE but potentiated the cytotoxicity of PE. Another energy inhibitor, salicylic acid, also protected cells from DE but had no effect with PE. Colchicine and colcemid did not affect the cytotoxicity of either toxin. Cytochalasin B exhibited a modest protection from DE but no effect with PE. Ouabain, a specific inhibitor of the Na+, K+-dependent adenosine 5'-triphosphatase (ATPase), did not affect the cytotoxicity of either toxin. Ruthenium red, a specific inhibitor of the Ca2+, Mg2+,-dependent ATPase, conferred marked protection from DE-induced cytotoxicity but did not affect PE-induced cytotoxicity. A number of local anesthetics were tested, and they too presented differential results with PE and DE. Most chemicals that affected toxin-induced cytotoxicity had little or no influence on the in vitro adenosine 5'-diphosphate-ribosylation catalyzed by either toxin. This work presents further evidence that PE and DE have different mechanisms of intoxication and suggests that these differences lie in the attachment or internalization stages of intoxication.
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PMID:Differential chemical protection of mammalian cells from the exotoxins of Corynebacterium diphtheriae and Pseudomonas aeruginosa. 14 24

Anions exert an influence on the passive permeability of Na+ and K+ in erythrocytes. THE EFFECT ON Mg-ATPase activity has been studied in human erythrocytes. 40 mM bicarbonate increased the activity as compared to the effect of 40 mM chloride; 20 mM sulphate inhibited it. Salicylate acted first as an activator then as an inhibitor of Mg-ATPase; maximum activity was reached at 60 mM CONCENTRATION. Thiocyanate inhibited saponin-stimulated Mg-ATPase, Ki = 1.85 X 10(-2)M. The probable mechanisms of action of the above anions on Mg-ATPase and possible relation to passive permeability of Na+ and K+ ions are discussed.
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PMID:The effect of anions on Mg-ATPase in red blood cells. 14 97

The components of the proton motive force (Deltap), namely, membrane potential (Deltapsi) and transmembrane pH gradient (DeltapH), were determined in the nitrifying bacteria Nitrosomonas europaea and Nitrobacter agilis. In these bacteria both Deltapsi and DeltapH were dependent on external pH. Thus at pH 8.0, Nitrosomonas europaea and Nitrobacter agilis had Deltapsi values of 173 mV and 125 mV (inside negative), respectively, as determined by the distribution of the lipophilic cation [(3)H]tetraphenyl phosphonium. Intracellular pH was determined by the distribution of two weak acids, (14)C-benzoic and (14)C-acetyl salicylic, and the weak base [(14)C]methylamine. Nitrosomonas europaea accumulated (14)C-benzoic acid and (14)C-acetyl salicylic acid when the external pH was below 7.0 and [(14)C]methylamine at alkaline pH. Similarly, Nitrobacter agilis accumulated the two weak acids below an external pH of about 7.5 and [(14)C]methylamine above this pH. As these bacteria grow best between pH 7.5 and 8.0, they do not appear to have a DeltapH (inside alkaline). Thus, above pH 7.0 for Nitrosomonas europaea and pH 7.5 for Nitrobacter agilis, Deltapsi only contributed to Deltap. In Nitrosomonas europaea the total Deltap remained almost constant (145 to 135 mV) when the external pH was varied from 6 to 8.5. In Nitrobacter agilis, Deltap decreased from 178 mV (inside negative) at pH 6.0 to 95 mV at pH 8.5. Intracellular pH in Nitrosomonas europaea varied from 6.3 at an external pH of 6.0 to 7.8 at external pH 8.5. In Nitrobacter agilis, however, intracellular pH was relatively constant (7.3 to 7.8) over an external pH range of 6 to 8.5. In Nitrosomonas europaea, Deltap and its components (Deltapsi and DeltapH) remained constant in cells at various stages of growth, so that the metabolic state of cells did not affect Deltap. Such an experiment was not possible with Nitrobacter agilis because of low cell yields. The effects of protonophores and ATPase inhibitors on DeltapH and Deltapsi in the two nitrifying bacteria are considered.
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PMID:Proton electrochemical gradients in washed cells of Nitrosomonas europaea and Nitrobacter agilis. 683 87

Highly purified lysosomes, prepared by magnetic fractionation of homogenates from Dictyostelium discoideum cells fed colloidal iron, were lysed under hypoosmotic conditions, and the membrane-associated proteins were subjected to gel electrophoresis. Thirteen major membrane polypeptides, ranging in molecular weight from 25,000 to 100,000 were identified. The isoelectric points of these proteins ranged from below 3.8 to greater than 7.0. Most of these proteins were stripped from membranes exposed to a chaotropic agent, 3,5-diodo-2-hydroxybenzoic acid lithium salt, and were therefore classified as peripheral membrane proteins. Twenty five glycoprotein species were detected by lectin blot analysis; 19 were classified as integral membrane proteins, and were, in general, larger than 45 kDa and negatively charged due in part to the presence of mannose 6-sulfate. Western blot analysis also demonstrated that a Rab 4-like GTPase, a Rab 7-like GTPase, and at least three subunits of the vacuolar ATPase were associated with the lysosomal membrane; the ATPase subunits appeared to be major proteins in lysosomal membranes. Finally, based on N-terminal sequence analysis of a major 41-kDa lysosome-associated membrane protein, we cloned a cDNA that encodes a protein (DVA41) highly homologous to a yeast and a bovine vacuolar ATPase subunit of approximately 41 kDa. The D. discoideum DVA41 gene was apparently a single copy gene, expressed at constant levels during growth and development.
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PMID:Characterization of lysosomal membrane proteins of Dictyostelium discoideum. A complex population of acidic integral membrane glycoproteins, Rab GTP-binding proteins and vacuolar ATPase subunits. 792 76

Nitrate transport in Aspergillus nidulans was dependent upon a consistent proton motive force (delta p) across the cell membrane which was maintained in a range of 105 (+/- 6.7) to 131 (+/- 3.4) mV over an external pH span of 5.5 to 7.5. The membrane potential (delta psi) measured by uptake of [3H]-tetra-phenylphosphonium bromide and the transmembrane pH difference (delta pH) measured by the distribution of 3H2O and [14C]- salicylic acid were used to compute the delta p present during transport of nitrate. Energy dependent accumulation of nitrate was measured in actively assimilating and tungstate inhibited cells. A delta G for nitrate of 14 kJ mol-1 was computed from the results. Cells induced for nitrate transport maintained internal nitrate levels of 6 to 8 mM based on an internal volume of 2.6 microliters/mg dry wt as determined by a conventional dual label procedure. A fivefold higher level of cellular nitrate was observed in tungstate inhibited cells. Nitrate accumulation was dependent upon a H+ gradient which was dissipated by treatment with 2-butanol, the ionophores valinomycin and gramicidin and the proton conductors carbonyl cyanide m-chlorophenyl hydrazone and N,N'-dicyclo-hexylcarbodiimide. Significant ATP and nitrate efflux occurred in cells treated with the above agents. The results suggest that nitrate is transported by symport with H+ on a carrier which is functionally linked to a H+ ATPase pump.
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PMID:Evidence for a H+ nitrate symporter in Aspergillus nidulans. 802 7

Systemin is an important mediator of wound-induced defense gene activation in tomato plants, and it elicits a rapid alkalinization of the growth medium of cultured Lycopersicon peruvianum cells. A possible mechanistic link between proton fluxes across the plasma membrane and the induction of defense genes was investigated by modulating plasma membrane H+-ATPase activity. Inhibitors of H+-ATPase (erythrosin B, diethyl stilbestrol, and vanadate) were found to alkalinize the growth medium of L. peruvianum cell cultures and to induce wound response genes in whole tomato plants. Conversely, an activator of the H+-ATPase (fusicoccin) acidified the growth medium of L. peruvianum cell cultures and suppressed systemin-induced medium alkalinization. Likewise, in fusicoccin-treated tomato plants, the wound- and systemin-triggered accumulation of wound-responsive mRNAs was found to be suppressed. However, fusicoccin treatment of tomato plants led to the accumulation of salicylic acid and the expression of pathogenesis-related genes. Apparently, the wound and pathogen defense signaling pathways are differentially regulated by changes in the proton electrochemical gradient across the plasma membrane. In addition, alkalinization of the L. peruvianum cell culture medium was found to depend on the influx of Ca2+ and the activity of a protein kinase. Reversible protein phosphorylation was also shown to be involved in the induction of wound response genes. The plasma membrane H+-ATPase as a possible target of a Ca2+-activated protein kinase and its role in defense signaling are discussed.
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PMID:Modulation of plasma membrane H+-ATPase activity differentially activates wound and pathogen defense responses in tomato plants. 992 43

Treatment of tomato plants (Lycopersicon esculentum Mill.) with fusicoccin (FC), an activator of the plasma-membrane H+-ATPase which maintains an electrochemical gradient across the plasma membrane, resulted in a dose-dependent accumulation of transcripts for intra- and extracellular pathogenesis-related (PR) proteins. The accumulation of PR protein transcripts was paralleled by an increase in leaf salicylic acid (SA) content. Transcripts of PR proteins and SA started to accumulate 3 h after FC treatment. 2-Aminoindan-2-phosphonic acid, an inhibitor of SA synthesis, was used to assess the role of SA in FC-mediated induction of PR gene expression. 2-Aminoindan-2-phosphonic acid was found to suppress the accumulation of SA but not the induction of PR gene expression in response to FC treatment. Furthermore, in transgenic tobacco plants overexpressing a bacterial salicylate hydroxylase gene (nahG-tobacco), PR transcripts accumulated after FC treatment to levels similar to those observed in control tobacco plants. The data indicate a role for the proton gradient across the plasma membrane in the SA-independent induction of PR gene expression.
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PMID:Salicylic acid-independent induction of pathogenesis-related gene expression by fusicoccin. 1078 53

Salicylic acid (SA), an endogenous signaling molecule of plants, possesses anti-inflammatory and anti-neoplastic actions in human. Its derivative, aspirin, is the most commonly used anti-inflammatory and analgesic drug. Aspirin and sodium salicylate (salicylates) have been reported to have multiple pharmacological actions. However, it is unclear whether they bind to a cellular protein. Here, we report for the first time the purification from human fibroblasts of a approximately 78 kDa salicylate binding protein with sequence identity to immunoglobulin heavy chain binding protein (BiP). The Kd values of SA binding to crude extract and to recombinant BiP were 45.2 and 54.6 microM, respectively. BiP is a chaperone protein containing a polypeptide binding site recognizing specific heptapeptide sequence and an ATP binding site. A heptapeptide with the specific sequence displaced SA binding in a concentration-dependent manner whereas a control heptapeptide did not. Salicylates inhibited ATPase activity stimulated by this specific heptapeptide but did not block ATP binding or induce BiP expression. These results indicate that salicylates bind specifically to the polypeptide binding site of BiP in human cells that may interfere with folding and transport of proteins important in inflammation.
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PMID:Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts. 1168 71

Fusicoccin (FC), an activator of the plant plasma membrane H+-ATPase, induces several components of plant pathogen resistance responses, including defence hormone biosynthesis and pathogenesis-related (PR) gene expression. The mechanism by which these responses occur, and the effect they have on plant-pathogen interactions is unknown. Here, we show that PR gene expression in response to FC in tomato (Lycopersicon esculentum Mill.) plants does not strictly require the common defence hormones, salicylic acid, jasmonic acid and ethylene. We also show that FC-induced PR gene expression requires neither Ca2+ nor reactive oxygen species, typical early pathogen-resistance response signals. The possibility that PR gene expression is related to FC-induced dehydration stress is also discounted. Finally, we show that the defence responses elicited by FC in tomato are not sufficient to confer resistance to the bacterial pathogen Pseudomonas syringae. Rather, FC increases the rate and severity of disease symptom formation in an ethylene-dependent manner.
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PMID:Fusicoccin activates pathogen-responsive gene expression independently of common resistance signalling pathways, but increases disease symptoms in Pseudomonas syringae-infected tomato plants. 1501 97


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