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

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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)

Agents that can arrest cellular proliferation are now providing insights into mechanisms of growth factor action and how this action may be controlled. It is shown here that the macrophage activating agents tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), and lipopolysaccharide (LPS) can maximally inhibit colony stimulating factor-1 (CSF-1)-induced, murine bone marrow-derived macrophage (BMM) DNA synthesis even when added 8-12 h after the growth factor, a period coinciding with the G1/S-phase border of the BMM cell cycle. This inhibition was independent of autocrine PGE2 production or increased cAMP levels. In order to compare the mode of action of these agents, their effects on a number of other BMM responses in the absence or presence of CSF-1 were examined. All three agents stimulated BMM protein synthesis; TNF alpha and LPS, but not IFN gamma, stimulated BMM Na+/H+ exchange and Na+,K(+)-ATPase activities, as well as c-fos mRNA levels. IFN gamma did not inhibit the CSF-1-induced Na+,K(+)-ATPase activity. TNF alpha and LPS inhibited both CSF-1-stimulated urokinase-type plasminogen activator (u-PA) mRNA levels and u-PA activity in BMM, whereas IFN gamma lowered only the u-PA activity. In contrast, LPS and IFN gamma, but not TNF alpha, inhibited CSF-1-induced BMM c-myc mRNA levels, the lack of effect of TNF alpha dissociating the inhibition of DNA synthesis and decreased c-myc mRNA expression for this cytokine. These results indicate that certain biochemical responses are common to both growth factors and inhibitors of BMM DNA synthesis and that TNF alpha, IFN gamma, and LPS, even though they all have a common action in suppressing DNA synthesis, activate multiple signaling pathways in BMM, only some of which overlap or converge.
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PMID:Biochemical events accompanying macrophage activation and the inhibition of colony-stimulating factor-1-induced macrophage proliferation by tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide. 133 37

Toxoplasma gondii, the etiologic agent of toxoplasmosis, is a ubiquitous protozoan parasite that requires an intracellular site for growth and replication. The invasive process involves six steps: a) cellular recognition, b) parasite movements by means of a subpellicular microtubule cytoskeleton, c) cell to cell adhesion, d) rhoptry secretion of penetrating enhancing factor (PEF) with Ca++ and Ca++ activated ATPase dependence, e) conoid penetration, f) induction of a parasitophorous vacuole, a protective and exchange site, interiorization of the parasite. The invasion is an active, oriented and specific process depending on chemical factors as energy sources, cations, as well as microviscosity and membrane structures. Toxoplasma gondii stimulates T cell subsets and induces lymphokine (IFN gamma, IL2) release.
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PMID:Review: Toxoplasma gondii cellular invasion. 133 76

In this report it has been shown that inhibition of the 2-5A synthetase in IFN-treated, vaccinia virus-infected mouse L and human HeLa S3 cells is related to specific viral functions. This inhibition occurs concomitantly with degradation of ATP and with dephosphorylation of ppp(A2'p)nA. At least two viral-mediated enzyme activities are thought to be involved in this process, an ATPase and a phosphatase. The ATPase activity was established after determining the extent of hydrolysis of ATP, the nature of 2-5A, and the relative abundance of the different oligomers. Cytoplasmic cell extracts and purified vaccinia virions were bound to poly (I):(C) agarose, incubated with [3H]ATP, [alpha-32P]ATP, or [gamma-32P]ATP, and the extent of hydrolysis of ATP was determined by TLC. Authentic 2-5A and the relative abundance of the various oligomers were characterized by enzymatic and alkali treatments and identification by TLC and HPLC analysis. The phosphatase activity was measured by TLC after determining the degree of dephosphorylation of 2-5A from the extent of labeling at the 5'-OH termini with [gamma-32P]ATP and polynucleotide kinase. While free 5'-OH termini were not observed in oligomers synthesized with bound poly (I):(C) agarose enzyme fractions from IFN-treated, uninfected cells, a strong phosphorylation was found in oligomers from IFN-treated, infected cells. These findings suggest that it is the contribution of these viral enzyme activities that renders vaccinia virus resistant to interferons.
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PMID:Nature and mode of action of vaccinia virus products that block activation of the interferon-mediated ppp(A2'p)nA-synthetase. 632 75

An inducible nitric oxide synthase has recently been described in proximal tubule epithelium. To investigate the effects of proximal tubule NO on Na+/K(+)-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity. Na+/K(+)-ATPase activity decreased after 4 h of LPS/IFN gamma treatment, reaching maximal inhibition after 24 h (34% reduction in activity). The inhibition of Na+/K(+)-ATPase activity by LPS/IFN gamma was prevented by simultaneous incubation with N omega-nitro L-arginine and markedly blunted by removal of L-arginine from the medium. The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K(+)-ATPase activity to a similar extent than LPS/IFN gamma. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K(+)-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K(+)-ATPase activity, suggesting a role for peroxynitrite in this inhibition. We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport.
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PMID:Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells. 753 54

We have used RNA differential display to identify specific mRNA species that are regulated by interferon-gamma (IFN gamma) treatment of enriched astrocyte cultures. Following a 24-hour treatment with IFN, mRNA was subjected to differential display using 15 different random primers. 105 upregulated and 5 downregulated cDNAs were selected for further sequencing and identification. Northern blot analysis confirmed the upregulation of 13 genes identical or highly similar to: intercrine adrenomedullin, H-rev 107, CAP-like protein, ATP synthase epsilon-subunit, complement C3, S-100 beta, Ca2+ ATPase, mg11, IFN-upregulated 56-kD protein mRNA, laminin receptor-like protein, protein tyrosine phosphatase, and zic. These data suggest that exposure to IFN gamma results in a complex change in the pattern of astrocyte gene expression.
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PMID:Identification of mRNAs regulated by interferon-gamma in cultured rat astrocytes by PCR differential display. 884 Mar 37

We have shown previously that interferon-beta (IFN-beta) induces the alkalinization of trans-Golgi network (TGN) and inhibits the transport of G protein of vesicular stomatitis virus (VSV) in L(B) cells and gD protein of herpes simplex virus (HSV-1) in LMtk- cells transfected with gD cDNA. The vacuolar H(+)-ATPase (V-ATPase) is responsible for maintaining pH in TGN, and V-ATPase-mediated acidification is required for normal transport of proteins. To examine whether alkalinization caused by IFN is mediated through V-ATPase, the activity of V-ATPase was determined in IFN-treated cells by coupling ATP hydrolysis to NADH oxidation. Bafilomycin (Baf) was used as positive control, as it specifically inhibits V-ATPase. The activity of V-ATPase was reduced in IFN-treated or Baf-treated cells compared with untreated cells. Doses of IFN-beta or Baf that neither alter pHi nor inhibit the transport of viral glycoproteins concomitantly inhibited the transport of G and gD proteins in TGN, as demonstrated by indirect immunofluorescence studies, and raised the pH of TGN as demonstrated by a decrease in the uptake of DAMP. Further, the effect of Baf on IFN-induced antiviral activity against VSV was examined to correlate the biologic significance of these findings. Data showed that Baf significantly enhances (5-50-fold) the IFN-induced antiviral activity as demonstrated by viral titers from supernatants. These findings suggest that the inhibition of transport of G and gD proteins by IFN-beta, may be related to the inhibition of V-ATPase-mediated acidification of TGN.
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PMID:Role of vacuolar H(+)-ATPase in interferon-induced inhibition of viral glycoprotein transport. 1057 23

In mammalian cells proteasomes can be activated by two different types of regulatory complexes which bind to the ends of the proteasome cylinder. Addition of two 19 S (PA700; ATPase) complexes forms the 26 S proteasome, which is responsible for ATP-dependent non-lysosomal degradation of intracellular proteins, whereas 11 S complexes (PA28; REG) have been implicated in antigen processing. The PA28 complex is upregulated in response to gamma-interferon (gamma-IFN) as are three non-essential subunits of the 20 S proteasome. In the present study we have investigated the effects of gamma-IFN on the level of different proteasome complexes and on the phosphorylation of proteasome subunits. After treatment of cells with gamma-IFN, the level of 26 S proteasomes decreased and there was a concomitant increase in PA28-proteasome complexes. However, no free 19 S regulatory complexes were detected. The majority of the gamma-IFN-inducible proteasome subunits LMP2 and LMP7 were present in PA28-proteasome complexes, but these subunits were also found in 26 S proteasomes. The level of phosphorylation of both 20 S and 26 S proteasome subunits was found to decrease after gamma-IFN treatment of cells. The C8 alpha subunit showed more than a 50% decrease in phosphorylation, and the phosphorylation of C9 was only barely detectable after gamma-IFN treatment. These results suggest that association of regulatory components to 20 S proteasomes is regulated, and that phosphorylation of proteasome alpha subunits may be one mode of regulation.
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PMID:gamma-Interferon decreases the level of 26 S proteasomes and changes the pattern of phosphorylation. 1113 93

Interference of thapsigargin (TG), an inhibitor of endoplasmic reticulum Ca(2+) ATPase, with immune reactivity of murine macrophages was investigated under conditions in vitro. The activation of cells with lipopolysaccharide (LPS), interferon-(gamma) (IFN-(gamma)), and with acyclic nucleoside phosphonate N(6)-isobutyl-9-[2-(phosphonomethoxy)ethyl]- 2,6-diaminopurine (N(6)-isobutyl-PMEDAP) resulted in enhanced production of cytokines TNF-alpha, IL-10, chemokines RANTES/CCL5 and MIP-1alpha/CCL3, as well as in substantially augmented production of nitric oxide (NO) triggered by IFN-(gamma). The effects were in a dual mode of action influenced by TG (1 microM). While TG upregulated secretion of TNF-alpha, it inhibited secretion of IL-10 and RANTES. The immune-stimulated secretion of MIP-1alpha remained virtually unaffected, though TG on its own activated expression of MIP-1alpha in macrophages. The high-output NO production induced by IFN-(gamma), high concentrations of LPS, or by combination of IFN-(gamma) plus LPS or N(6)-isobutyl-PMEDAP was inhibited by TG. On the other hand, production of NO which was marginally activated by low concentration of LPS was upregulated by TG.
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PMID:Modulator of intracellular Ca(2+), thapsigargin, interferes with in vitro secretion of cytokines and nitric oxide. 1660 80

The ATPase retinoid acid-inducible gene (RIG)-I senses viral RNA in the cytoplasm of infected cells and subsequently activates cellular antiviral defense mechanisms. RIG-I recognizes molecular structures that discriminate viral from host RNA. Here, we show that RIG-I ligands require base-paired structures in conjunction with a free 5'-triphosphate to trigger antiviral signaling. Hitherto unavailable chemically synthesized 5'-triphosphate RNA ligands do not trigger RIG-I-dependent IFN production in cells, and they are unable to trigger the ATPase activity of RIG-I without a base-paired stretch. Consistently, immunostimulatory RNA from cells infected with a virus recognized by RIG-I is sensitive to double-strand, but not single-strand, specific RNases. In vitro, base-paired stretches and the 5'-triphosphate bind to distinct sites of RIG-I and synergize to trigger the induction of signaling competent RIG-I multimers. Strengthening our model of a bipartite molecular pattern for RIG-I activation, we show that the activity of supposedly "single-stranded" 5'-triphosphate RNAs generated by in vitro transcription depends on extended and base-paired by-products inadvertently, but commonly, produced by this method. Together, our findings accurately define a minimal molecular pattern sufficient to activate RIG-I that can be found in viral genomes or transcripts.
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PMID:5'-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. 1957 55

Inappropriate activation of TLR9 has been found to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. TLR9 antagonists have been proposed to be therapeutic for some kinds of autoimmune diseases. In contrast, new negative regulators of TLR9 signal pathway need to be identified, and the mechanisms for the control of TLR9 response need to be fully investigated. It is well known that TLR9 will be finally transported to late endosome/lysosome once activated; however, the exact mechanism and the biological significance of the redistribution have not been fully elucidated. Ras related in brain (Rab)7b is a small guanosine triphosphatase, identified by us before, which is mainly localized in late endosome/lysosome. Our previous study shows that Rab7b can negatively regulate TLR4 signaling by promoting lysosomal degradation of TLR4. In this study, we show that TLR9 ligation can inhibit Rab7b expression in macrophages via ERK and p38 activation. In turn, the late endosome/lysosome-localized Rab7b can colocalize with TLR9 in lysosomal-associated membrane protein 1-positive compartment and down-regulate the expression of the TLR9 in macrophages by promoting TLR9 degradation once TLR9 is activated. Accordingly, Rab7b can negatively regulate TLR9-triggered production of TNF-alpha, IL-6, and IFN-beta in macrophages by impairing activation of MAPKs and NF-kappaB pathways. Our results suggest that the late endosome/lysosome-localized Rab7b can down-regulate TLR9-triggered proinflammatory cytokine and type I IFN production by impairing TLR9 signaling via promotion of TLR9 degradation.
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PMID:Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages. 1958 7


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