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)

Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. cPrG.HCl markedly suppressed 3H-thymidine incorporation by concanavalin A stimulated murine splenocytes but had little effect on lipopolysaccharide dependent 3H-thymidine incorporation, indicating that cPrG.HCl acts as a selective inhibitor of T cell proliferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cells through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membranes without any effect on either its ATPase activity nor on the membrane conductance of phospholipid bilayers, suggesting that cPrG.HCl selectively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is highly stable, it raises the possibility of its therapeutic use as an immunosuppressant.
...
PMID:A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans. 929

The possibility that diacylglycerol analogues might have a wider spectrum of intracellular targets than the well-known protein kinase C was investigated with vesicles containing the Ca2+-ATPase derived from the dense tubular system in platelets and from the sarcoplasmic reticulum of skeletal muscle. The diacylglycerol analogues PMA and 1-oleoyl-2-acetyl-rac-glycerol (OAG) inhibited Ca2+ accumulation by these vesicles, an effect that was antagonized by cyclosporin A. The inhibitory activity of PMA and OAG resulted from the uncoupling of the Ca2+-ATPase, characterized by a pronounced inhibition of Ca2+ uptake accompanied by a discrete decrease in ATPase activity and by the inhibition of the enzyme's phosphorylation by Pi, leading to both a decrease in ATP synthesis and an enhancement of Ca2+ efflux. The inhibition of Ca2+ uptake by PMA was found to decrease as the Ca2+ concentration in the medium was raised from 0.1 to 10.0 microM. This was observed with muscle, but not with platelet vesicles. In contrast, the ability of cyclosporin A to antagonize the inhibition of Ca2+ uptake by PMA also increased when the Ca2+ concentration in the medium was raised from 0.1 to 10.0 microM, but this was observed with both muscle and platelet vesicles. The fact that phospholipase C activity and products from the inositol metabolism have been described as localized in regions of the sarcoplasmic reticulum where Ca2+-ATPase and Ca2+ channels are found suggests a possible physiological role for these products in the regulation of cytosolic Ca2+ levels.
...
PMID:Uncoupling of Ca2+ transport ATPase in muscle and blood platelets by diacylglycerol analogues and cyclosporin A antagonism. 958 58

Glial cells extrude acid equivalents to maintain pHi. Although four mechanisms have been described so far, pHi-control under physiological conditions is still not sufficiently explained. We therefore investigated whether a H+-translocating ATPase is involved in glial pHi homeostasis using an established glial cell line (C6 glioma). In the absence of bicarbonate, the inhibition of H+-ATPases by NEM led to a pHi decrease. The application of a more specific inhibitor (NBD-Cl) showed that the H+-ATPase involved is of the vacuolar type. Inhibition went along with delayed cell swelling. Together with the fact that glial acidification was far more pronounced in Na+-free media, this may serve as evidence for a secondary activation of Na+/H+-exchange once an activation setpoint is reached, which in turn causes secondary swelling from Na+-uptake. Stimulation of Na+/H+-exchange by PMA can increase the setpoint. pHi-recovery after an acid load was blocked by the inhibition of v-type H+-ATPase, if pHi did not reach 6.6 during the acid load. The inhibition of Na+/H+-exchange by amiloride inhibited recovery only if acidification was below the threshold. Finally, in bicarbonate-free media a v-type H+-ATPase contributes to pH-regulation in glial cells, especially during pH-homeostasis at physiological conditions, while Na+/H+-exchange gains significance during severe acid loads.
...
PMID:A proton-translocating H+-ATPase is involved in C6 glial pH regulation. 965 71

Scrape loading Clostridium botulinum C3 exoenzyme into primary peripheral blood human T lymphocytes (PB T cells) efficiently adenosine diphosphate (ADP)-ribosylates and thus inactivates the guanosine triphosphatase (GTPase) Rho. Basal adhesion of PB T cells to the beta1 integrin substrate fibronectin (Fn) was not inhibited by inactivation of Rho, nor was upregulation of adhesion using phorbol myristate acetate (PMA; 10 ng/ml) or Mn++ (1 mM) affected. Whereas untreated PB T cells adherent to Fn remain spherical, C3-treated PB T cells extend F-actin-containing pseudopodia. Inactivation of Rho delayed the kinetics of PMA-dependent PB T cell homotypic aggregation, a process involving integrin alphaLbeta2. Although C3 treatment of PB T cells did not prevent adhesion to the beta1 integrin substrate Fn, it did inhibit beta1 integrin/CD3-mediated costimulation of proliferation. Analysis of intracellular cytokine production at the single cell level demonstrated that ADP-ribosylation of Rho inhibited beta1 integrin/ CD3 and CD28/CD3 costimulation of IL-2 production within 6 h of activation. Strikingly, IL-2 production induced by PMA and ionomycin was unaffected by C3 treatment. Thus, the GTPase Rho is a novel regulator of T lymphocyte cytoarchitecture, and functional Rho is required for very early events regulating costimulation of IL-2 production in PB T cells.
...
PMID:Adenosine diphosphate (ADP)-ribosylation of the guanosine triphosphatase (GTPase) rho in resting peripheral blood human T lymphocytes results in pseudopodial extension and the inhibition of T cell activation. 976

Using SK-N-SH cells, we observe that muscarinic acetylcholine receptor activation by methacholine (MCh) rapidly and selectively diminishes l-NE transport capacity (Vmax) with little or no change in norepinephrine (NE) Km and without apparent effects on membrane potential monitored directly under current clamp. Over the same time frame, MCh exposure reduces the density of [3H]nisoxetine binding sites (Bmax) in intact cells but not in total membrane fractions, consistent with a loss of transport capacity mediated by sequestration of transporters rather than changes in intrinsic transport activity or protein degradation. Similar changes in NE transport and [3H]nisoxetine binding capacity are observed after phorbol ester (beta-PMA) treatment. Inhibition of PKC by antagonists and downregulation of PKC by chronic treatment with phorbol esters abolishes beta-PMA-mediated effects but produce only a partial blockade of MCh-induced effects. Neither muscarinic acetylcholine receptor nor PKC activation require extracellular Ca++ to diminish NET activity. In contrast, treatment of cells with the Ca++/ATPase antagonist, thapsigargin in Ca++-free medium, eliminates the staurosporine-insensitive component of MCh regulation. These findings were further corroborated by the ability of [1, 2-bis(o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester application in Ca++-free medium to abolish NET regulation by MCh. Although they may contribute to basal NET expression, we could not implicate CaMKII-, PKA- or nitric oxide-linked pathways in MCh regulation. Together, these findings 1) provide evidence in support of G-protein coupled receptor-mediated regulation of catecholamine transport, 2) reveal intracellular Ca++-sensitive, PKC-dependent and -independent pathways that serve to regulate NET expression and 3) indicate that the diminished capacity for NE transport evident after mAChR and PKC activation involves a redistribution of NET protein.
...
PMID:Acute regulation of norepinephrine transport: I. protein kinase C-linked muscarinic receptors influence transport capacity and transporter density in SK-N-SH cells. 980 4

In a series of experiments aimed to understand the signaling pathways that regulate intracellular pH (pHi) in rat mast cells, the effect of different intracellular mechanisms on the activity of the Na+/H+ exchanger was studied. After promoting an artificial acidification with sodium propionate we determined the variations on pHi rate recovery. pHi was measured with the dye 2, 7-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester. We studied the effect that the inhibition of some cellular exchangers with different drugs induced on pHi. When the Na+/H+ exchanger was inhibited in the presence of amiloride, the recovery rate constant was twofold smaller than the control value. After the recovery, the final pH was lower than the initial value when the cells were treated either with amiloride or with 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (an anionic antiport inhibitor). No effect was observed when the Na+/K+-ATPase or the Na+/Ca2+ exchanger were inhibited. The suppression of intracellular and extracellular calcium did not induced any change in pHi. The addition of thapsigargin, an activator of capacitative calcium influx, or the phorbol esther 12-O-tetradecanoylphorbol-13-acetate (PMA), a protein kinase C (PKC) activator, increased the activity of the antiporter. Both effects were abrogated by inhibition of the Na+/K+-ATPase with ouabain. The increase in cAMP levels did not affect the effect of PMA on pHi recovery, but it blocked the effect of thapsigargin. Our results indicate that rat mast cells regulate pHi by the combination of some anionic exchanger and the Na+/H+ antiporter. And also that the modulation of this exchanger is the consequence of the connection between different intracellular mechanisms, Na+/K+-ATPase-PKC-calcium, among which cAMP seems not to have a direct role.
...
PMID:Sodium, PMA and calcium play an important role on intracellular pH modulation in rat mast cells. 994 57

Changes of [Ca2+]i in CCL229 cells induced by retionoic acid (RA), 1,25(OH)2VD3 and PMA were measured by spectrofluorometry. The effects of endoplasmic reticulum (ER)-specific Ca(2+)-ATPase inhibitor thapsigargin (TG) and IP3 receptor inhibitor heparin on RA-induced changes of [Ca2+]i were observed and the relationship between RA-induced changes of [Ca2+]i and ER was also investigated. The results showed that [Ca2+]i increased markedly in several seconds after treated by RA and 1,25(OH)2VD3. When cells were pretreated with EGTA and verapamil (Ca2+ entry blocker drug), TG could not inhibit RA-stimulated Ca2+ release from intracellular calcium pools and TG could increase [Ca2+]i after pretreated by RA. In addition, heparin could not completely inhibit RA-induced [Ca2+]i increase. The results suggest that RA might stimulate IP3-sensitive pool or IP3-insensitive pool on ER to increase [Ca2+]i, or there might be RA-sensitive calcium pools except ER in cells.
...
PMID:[Changes of [Ca2+]i in colorectal cancer cells induced by some chemicals]. 1007 20

The relation between degranulation and rapid metabolic responses (acidification rate changes) in RBL-2H3 cells was studied using a cytosensor microphysiometer, a silicon-based biosensor system. The metabolic responses in RBL-2H3 cells by antigen stimulation were compared with those by inhibitors of Ca2+ -ATPase. The former resulted in a rapid transient increase in the acidification rate of RBL-2H3 cells while the latter resulted in gradual decreases. When RBL-2H3 cells were costimulated with the inhibitors of Ca2+ -ATPase and an activator (PMA, phorbol-12-myristoyl-13-acetate) of protein kinase C, the metabolic responses increased again in RBL-2H3 cells. This seems to indicate that degranulation in RBL-2H3 cells was accelerated by costimulation with the inhibitors and PMA. However, costimulation was not able to completely mimic the way antigen stimulated RBL-2H3 cells in degranulation and in rapid metabolic responses.
...
PMID:The relation between degranulation and rapid metabolic responses in RBL-2H3 cells. 1022 Feb 90

Proliferation, differentiation, and survival of erythroid progenitor cells are mainly regulated by stem cell factor (SCF) and erythropoietin (Epo). Using normal human progenitors, we analyzed the role of Ca2+-sensitive protein kinase C (PKC) subtypes and of G-protein-coupled receptor ligands on growth factor-dependent DNA synthesis. We show that stimulation of DNA synthesis by the two growth factors requires activation of PKCalpha. Inhibitors of Ca2+-activated PKC subtypes blocked the growth factor-induced 3H-thymidine incorporation. SCF and Epo caused no significant translocation of PKCalpha into the membrane, but treatment of intact cells with either of the two cytokines resulted in enhanced activity of immunoprecipitated cytosolic PKCalpha. Stimulation of PKC with the phorbol ester PMA mimicked the cytokine effect on DNA synthesis. Epo-, SCF-, and PMA-induced thymidine incorporation was potently inhibited by thrombin (half-maximal inhibition with 0.1 U/mL). This effect was mediated via the G-protein-coupled thrombin receptor and the Rho guanosine triphosphatase. Adenosine diphosphate caused a modest Ca2+-dependent stimulation of DNA synthesis in the absence of cytokines and specifically enhanced the effect of SCF. Cyclic 3', 5'-adenosine monophosphate exerted a selective inhibitory effect on Epo-stimulated thymidine incorporation. Our results define PKCalpha as major intermediate effector of cytokine signaling and suggest a role for thrombin in controlling erythroid progenitor proliferation.
...
PMID:Erythropoietin- and stem cell factor-induced DNA synthesis in normal human erythroid progenitor cells requires activation of protein kinase Calpha and is strongly inhibited by thrombin. 1038 4

The N-terminus of the H(+)-ATPase from Saccharomyces cerevisiae contains a serine-rich cluster of 11 serine residues in the first 17 amino acids, including a stretch of eight consecutive serine residues. This cluster is conserved in the weakly expressed PMA2 gene from the same organism, but it is not present in PMA genes from other organisms suggesting that it is not likely to represent a conserved functional motif. To better understand whether this region plays a regulatory role, a series of mutant enzymes were generated in which the serine tract was systematically converted to alanine or deleted. Conversion of the first six serine residues to alanine or deletion of the entire serine tract had little effect on cell growth phenotypes. However, when eight or more serines were converted, the mutant cells displayed prominent hygromycin B-resistant and low pH-sensitive phenotypes indicative of reduced H(+)-ATPase function. The mutant enzymes were found to display relatively normal kinetic properties for ATP hydrolysis, but showed significantly decreased abundance in the plasma membrane under stress conditions when eight or more serine residues were converted to alanine. The reduced abundance of the enzyme appeared to be due to degradative turnover, as mutant enzymes with multiple alanine substitutions showed an accelerated rate of turnover relative to wild-type. The polyserine tract in the H(+)-ATPase does not appear to be important for catalysis, but may contribute to overall protein stability.
...
PMID:Modification of the N-terminal polyserine cluster alters stability of the plasma membrane H(+)-ATPase from Saccharomyces cerevisiae. 1044 4


<< Previous 1 2 3 4 5 6 7 Next >>

---