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)

A large amount of evidence points towards the potential role of lymphokine activated killer (LAK) cells as tools in the treatment of chronically stressed conditions, such as cancer. The modulation of this activity by biologically active endogenous compounds of the HPA (hypothalamic-pituitary-adrenal) axis, however, is not completely understood. Ouabain, a specific inhibitor of Na(+)-K(+)-ATPase, and now recognized as an endogenous component present in human plasma, was tested on IL-2 and TPA-activated killer cells. Ouabain was able to inhibit the generation of LAK activity, as well as to suppress either PHA or TPA-induced lymphocyte proliferation. Once the cells were triggered for cytotoxicity, however, ouabain was not able to interfere with their effector phase, as it did not show any effect when present only during the assay. TPA-induced "LAK-simile" cells displayed the same sensitivity towards ouabain as LAK cells did. Although the physiological relevance of endogenous ouabain secretion remains elusive, these effects of ouabain on LAK cytotoxicity should be considered in patients undergoing this kind of immunotherapy.
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PMID:Effect of ouabain on lymphokine-activated killer cells. 780 35

Rapamycin (RAPA) is a potent immunosuppressant. Several reports indicate that the drug can act at the late G1 stage of the lymphocyte activation. We studied the effect of RAPA on the expression of an immediate early phase gene c-jun, which plays a pivotal role in cell activation. The results showed that RAPA could inhibit PHA-induced c-jun expression by human T cells. This strongly suggests that there exists a mechanism for RAPA to interact with the lymphocyte activation cascade at a very early stage. We also demonstrated that in T cells a Na+/K+ ATPase inhibitor, ouabain, could induce a late (16 h poststimulation) c-jun expression, which was sensitive to cyclosporin A (CsA) but not to RAPA. This suggests that c-jun's role is probably not restricted to the early phase of lymphocyte activation.
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PMID:The effect of rapamycin on c-jun expression in human lymphocytes. 824 2

In Jurkat cells, the three Ca(2+)-ATPase blockers, thapsigargin, cyclopiazonic acid, and di-tert-butylhydroquinone (DtBuHQ) induced both a release of Ca2+ from intracellular stores and a Ca2+ influx. In contrast to CD3 mAb, the Ca(2+)-ATPase inhibitors did not induce the formation of inositol trisphosphate from the hydrolysis of phosphatidylinositides. Emptying intracellular Ca2+ stores was accompanied by a decrease of phosphatidylserine (PtdSer) synthesis as previously observed in PHA- or CD3 mAb-treated Jurkat cells. In the presence of a phorbol ester able to activate protein kinase C, TPA, the three Ca(2+)-ATPase inhibitors induced Jurkat cells to synthesize large amounts of interleukin-2 demonstrating that early signal transduction mechanisms can be bypassed by Ca(2+)-ATPase inhibitors. In purified human peripheral blood T lymphocytes, the same inhibitors induced moderate if any cytosolic Ca2+ rise, in the absence of external calcium. Nevertheless analysis of PtdSer synthesis suggested that intracellular stores were efficiently depleted by DtBuHQ and cyclopiazonic acid but not by thapsigargin. In contrast, the three compounds induced similar Ca2+ influx. However, in the presence of TPA, cyclopiazonic acid and DtBuHQ induce highly purified T cells to proliferate while thapsigargin did not, suggesting that the status of internal Ca2+ store may have a decisive role in T cell activation.
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PMID:Ca(2+)-ATPase inhibitors induce interleukin-2 synthesis and T cell proliferation. 833 Mar 10

Increase in Na+, K(+)-ATPase mRNAs was detected in activated lymphocytes by the RT-PCR method. alpha 1 subunit mRNA gradually increased with time and by 36 h was 2.4 times higher than at the start. Increase in the beta 1 mRNA was transient reaching a maximum in the 8 h probe and declining to the initial level in the 24 and 36 h probes. The elevation of Na+, K(+)-ATPase mRNAs does not underlie a cycloheximide-inhibited increase in cation pumping peculiar to the prereplicative period as can be judged from the fact that Act D fails to eliminate PHA-induced enhancement of pump fluxes.
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PMID:Expression of mRNAs encoding the alpha 1 and the beta 1 subunits of Na+, K(+)-ATPase in human lymphocytes activated with phytohaemagglutinine. 838 Jul 76

Apoptotic cell death plays a critical role in immune system homeostasis, and c-myc protooncogene deregulated expression is a component of this programmed genomic response. Pharmacological intervention and modulation of peripheral lymphocytes apoptosis would have important implications. The present results indicate that ouabain, a specific inhibitor of Na+K(+)-ATPase, promotes an increased expression of c-myc mRNA, and induces apoptosis in PHA-stimulated lymphocytes. Furthermore, this ouabain-induced apoptosis cannot be counteracted by the addition of exogenous IL-2.
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PMID:Ouabain induces apoptosis on PHA-activated lymphocytes. 965 13

This study presents the characterization of the plasma membrane (PM) H+-ATPases in potato, focusing on their role in stolon and tuber development. Seven PM H+-ATPase genes were identified in the Solanum tuberosum genome, designated PHA1-PHA7. PHA genes show distinct expression patterns in different plant tissues and under different stress treatments. Application of PM H+-ATPase inhibitors arrests stolon growth, promotes tuber induction, and reduces tuber size, indicating that PM H+-ATPases are involved in tuberization, acting at different stages of the process. Transgenic potato plants overexpressing PHA1 were generated (PHA1-OE). At early developmental stages, PHA1-OE stolons elongate faster and show longer epidermal cells than wild-type stolons; this accelerated growth is accompanied by higher cell wall invertase activity, lower starch content, and higher expression of the sucrose-H+ symporter gene StSUT1. PHA1-OE stolons display an increased branching phenotype and develop larger tubers. PHA1-OE plants are taller and also present a highly branched phenotype. These results reveal a prominent role for PHA1 in plant growth and development. Regarding tuberization, PHA1 promotes stolon elongation at early stages, and tuber growth later on. PHA1 is involved in the sucrose-starch metabolism in stolons, possibly providing the driving force for sugar transporters to maintain the apoplastic sucrose transport during elongation.
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PMID:The plasma membrane H+-ATPase gene family in Solanum tuberosum L. Role of PHA1 in tuberization. 2899 10

H-Ras is a guanosine triphosphatase (GTPase), which acts as a molecular switch and controls multiple important cellular processes including lymphocyte activation and function. However, regulatory mechanism of adaptive immune response by H-Ras remains unclear in non-mammalian animals. In the present study, we investigated the involvement of H-Ras in lymphocyte activation with a teleost model Oreochromis niloticus. H-Ras from O. niloticus (On-H-Ras) is highly conserved with those from other vertebrates. The mRNA of On-H-Ras showed a wide expression pattern in the lymphoid-tissues and with the highest level in liver. After Aeromonas hydrophila infection, transcription of On-H-Ras was significantly induced on day 8 but came back to basal level on day 16, suggesting that On-H-Ras potentially participated in primary response during the adaptive immunity. Furthermore, On-H-Ras mRNA was obviously up-regulated when leukocytes were activated by T lymphocyte mitogen PHA in vitro. Meanwhile, protein level of H-Ras was also augmented once leukocytes were stimulated with lymphocyte receptor signaling agonist PMA and ionomycin. More importantly, once Ras activity was inhibited by specific inhibitor, the up-regulation of lymphocyte activation marker CD122 was obviously impaired during lymphocyte activation process. Therefore, On-H-Ras regulated lymphocyte activation through both mRNA and protein level. Altogether, our results illustrated the involvement of H-Ras in teleost adaptive immunity via controlling lymphocyte activation, and thus provided a novel perspective to understand evolution of the lymphocyte-mediated adaptive immunity.
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PMID:Involvement of H-Ras in the adaptive immunity of Nile tilapia by regulating lymphocyte activation. 3095 81


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