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:2.4.2.30 (PARP)
13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of rho protein purified from pig brain cytosol with EDTA (3 mM) for 10 min at 30 degrees C inhibited its ADP-ribosylation by Clostridium botulinum C3 ADP-ribosyltransferase by more than 90%. The EDTA effect was not caused by alteration of C3. GDP or GDP beta S present during the pretreatment period completely prevented the decrease in ADP-ribosylation with half-maximal and maximal effects at 3 and 300 microM, respectively. GTP or GTP gamma S were less efficacious in preventing the decrease in ADP-ribosylation, but were more potent (half-maximal and maximal effects at 0.1 and 3 microM, respectively). [32P]ADP-ribose incorporated in pig brain rho by C3 was de-ADP-ribosylated by the enzyme in the presence of nicotinamide and at low pH. Concomitantly, [32P]NAD was formed. The pH optima for ADP-ribosylation and de-ADP-ribosylation were pH 7.5 and 5.5, respectively. De-ADP-ribosylation was most efficient with nicotinamide, less effective with 3-acetylpyridine and not observed with 3-aminopyridine, 4-aminopyridine, 4-acetylpyridine and isonicotinic acid. As observed for the ADP-ribosylation, the de-ADP-ribosylation by C3 was maximal with the GDP-bound form of rho and blocked after EDTA treatment.
...
PMID:ADP-ribosylation and de-ADP-ribosylation of the rho protein by Clostridium botulinum exoenzyme C3. Regulation by EDTA, guanine nucleotides and pH. 182 95

Membrane-associated tumor necrosis factor (TNF) and soluble TNF were compared as to their lytic activities, and as to the kinetics of their expression by macrophages activated with LPS and/or IFN-gamma in the presence or absence of cycloheximide. EL 4 tumor cells, resistant and sensitive to lysis by recombinant TNF or membrane-associated TNF (paraformaldehyde (PF)-fixed activated macrophages) were used as targets. In the presence of cycloheximide the TNF-resistant S-EL4 cells were lysed by both TNFs. PF-fixed macrophages was cytolytic after 1 hr activation but not after 3 or more hours of activation. Their activity was totally inhibited by anti-TNF antibodies and was a composite of transmembrane (integral) TNF and soluble TNF conjugated to macrophage membrane TNF receptors. Treatment of the macrophages with glycine pH 3.0 buffer dissociated the conjugated TNF without affecting the integral membrane TNF. When macrophages were activated with LPS +/- IFN-gamma in the presence of cycloheximide or activated just with IFN-gamma their activity after fixation with paraformaldehyde was no longer detected. Nonfixed macrophages under these conditions still remained cytotoxic. Tumor cell susceptibility to membrane-associated TNF activity, in contrast to recombinant (soluble) TNF, was greatly reduced in the presence of nicotinamide, an inhibitor of ADP-ribosyltransferase, suggesting that the mechanisms of lysis by these TNFs may be different. The lytic activity of both TNFs was found to be receptor-dependent in that tumor cells, whose TNF binding sites were "down-regulated" by TPA, were rendered resistant to lysis by both membrane-associated and soluble TNFs.
...
PMID:Cytolytic activities of activated macrophages versus paraformaldehyde-fixed macrophages; soluble versus membrane-associated TNF. 183 87

Glutamic acid-148, an active-site residue of diphtheria toxin identified by photoaffinity labeling with NAD, was replaced with aspartic acid, glutamine, or serine by directed mutagenesis of the F2 fragment of the toxin gene. Wild-type and mutant F2 proteins were synthesized in Escherichia coli, and the corresponding enzymic fragment A moieties (DTA) were derived, purified, and characterized. The Glu----Asp (E148D), Glu----Gln (E148Q), and Glu----Ser (E148S) mutations caused reductions in NAD:EF-2 ADP-ribosyltransferase activity of ca. 100-, 250-, and 300-fold, respectively, while causing only minimal changes in substrate affinity. The effects of the mutations on NAD-glycohydrolase activity were considerably different; only a 10-fold reduction in activity was observed for E148S, and the E148D and E148Q mutants actually exhibited a small but reproducible increase in NAD-glycohydrolytic activity. Photolabeling by nicotinamide-radiolabeled NAD was diminished ca. 8-fold in the E148D mutant and was undetectable in the other mutants. The results confirm that Glu-148 plays a crucial role in the ADP-ribosylation of EF-2 and imply an important function for the side-chain carboxyl group in catalysis. The carboxyl group is also important for photochemical labeling by NAD but not for NAD-glycohydrolase activity. The pH dependence of the catalytic parameters for the ADP-ribosyltransferase reaction revealed a group in DTA-wt that titrates with an apparent pKa of 6.2-6.3 and is in the protonated state in the rate-determining step.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Active-site mutations of diphtheria toxin: effects of replacing glutamic acid-148 with aspartic acid, glutamine, or serine. 198 Feb 8

NAD is hydrolyzed during incubation with isolated renal brush border membranes (BBM). The specific enzymatic mechanisms have not been identified apart from the activity of ADP-ribosyltransferase, which accounts for a very small proportion of the total hydrolysis. In the present study, an NAD-glycohydrolase (NGH) was identified in the renal BBM using the cyanide-addition assay to monitor hydrolysis of NAD at the nicotinamide-ribose bond. The production of nicotinamide and ADP-ribose, the expected reaction products, was determined by thin-layer chromatography. The NGH was enriched ninefold in the BBM fraction and accounted for 36% of the total rate of NAD hydrolysis by BBM enzymes at pH 7.4. Assay of NGH in sealed BBM vesicles subjected to osmotic shock indicated that about 23% of the NGH is exposed on the cytoplasmic surface of the BBM. The enzyme was inhibited by nicotinamide in vitro and also when the nicotinamide was administered in vivo, suggesting, indirectly, that the enzyme may play a role in mediating the effects of nicotinamide on BBM phosphate transport.
...
PMID:NAD-glycohydrolase in renal brush border membranes. 241 52

Treatment of platelets with a prostacyclin analogue, iloprost, decreased the cholera-toxin-induced ADP-ribosylation of membrane-bound Gs alpha (alpha-subunit of G-protein that stimulates adenylate cyclase; 42 kDa protein) and a cytosolic substrate (44 kDa protein) [Molina y Vedia, Reep & Lapetina (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5899-5902]. This decrease is apparently not correlated with a significant change in the quantity of membrane Gs alpha, as detected by two Gs alpha-specific antisera. This finding contrasts with the suggestion in a previous report [Edwards, MacDermot & Wilkins (1987) Br. J. Pharmacol. 90, 501-510], indicating that iloprost caused a loss of Gs alpha from the membrane. Our evidence points to a modification in the ability of the 42 kDa protein to be ADP-ribosylated by cholera toxin. This modification of Gs alpha might be related to its ADP-ribosylation by endogenous ADP-ribosyltransferase activity. Here we present evidence showing that Gs alpha was ADP-ribosylated in platelets that had been electropermeabilized and incubated with [alpha-32P]NAD+. This endogenous ADP-ribosylation of Gs alpha is inhibited by nicotinamide and stimulated by iloprost.
...
PMID:The effect of iloprost on the ADP-ribosylation of Gs alpha (the alpha-subunit of Gs). 247 20

Clostridium spiroforme iotalike toxin produced time- and concentration-dependent incorporation of ADP-ribose into homo-poly-L-arginine. Polyasparagine, polyglutamic acid, polylysine, and agmatine were poor substrates. Enzyme activity was associated with the light-chain polypeptide of the toxin. The heavy chain did not possess ADP-ribosyltransferase activity, nor did it enhance or inhibit activity of the light chain. In broken-cell assays, the toxin acted mainly on G-actin, rather than F-actin. A single ADP-ribose group was transferred to each substrate molecule (G-actin). The enzyme was heat sensitive, had a pH optimum in the range of 7 to 8, was inhibited by high concentrations of nicotinamide, and was reversibly denatured by urea and guanidine. Physiological levels of nucleotides (AMP, ADP, ATP, and ADP-ribose) and cations (Na+, K+, Ca2+, and Mg2+) were not very active as enzyme inhibitors. The toxin was structurally and functionally similar to Clostridium botulinum type C2 toxin and Clostridium perfringens iota toxin. When combined with previous findings, the data suggest that a new class of mono(ADP-ribosyl)ating toxins has been found and that these agents belong to a related and possibly homologous series of binary toxins.
...
PMID:Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity: identification of a novel class of ADP-ribosyltransferases. 252 Dec 14

Treatment of rat basophilic leukemia cell line (2H3) with interferon-alpha significantly increased intracellular histamine levels. On the other hand, the histidine content was decreased reciprocally by interferon in a dose-dependent manner. Concomitantly, the activity of histidine decarboxylase, the enzyme responsible for histamine synthesis, was augmented. The increase in histidine decarboxylase activity was partially abolished in co-incubation with inhibitors of ADP-ribosyltransferase, such as 3-aminobenzamide or nicotinamide. These results suggest the pivotal role of activation of histidine decarboxylase, presumably through ADP-ribosylation of the enzyme, in interferon-induced histamine synthesis.
...
PMID:Induction of histidine decarboxylase in rat basophilic leukemia cells by interferon and prevention of its effect in coincubation with ADP-ribosyltransferase inhibitors. 252 50

In cultured human epidermal cells exposure to the vesicant sulfur mustard (HD) causes a decrease of the NAD+ content, which depends on the dose and the time period between exposure to HD and NAD+ measurement. Presumably, this NAD+ loss is due to activation of the enzyme NAD:protein ADP-ribosyltransferase (ADPRT) and may lead to glycolysis inhibition, disturbance of energy metabolism, and eventually cell death. Since prevention of this NAD+ depletion could lead to cell survival, HD-exposed cultures have been incubated with nicotinamide, a precursor of NAD+ and an inhibitor of ADPRT. Although a reduction in NAD+ levels of the cultures can be prevented, the uptake of glucose, which was taken as a measure for cellular viability, appears to be inhibited in cultures in which the NAD+ levels are at the 100% level at 4 hr after exposure. Therefore, prophylactic or therapeutic measures that are focused on maintenance of NAD+ levels in order to preserve energy supplies do not protect human epidermal cells in culture that have been exposed to HD. These experiments indicate that mechanisms other than NAD+ depletion may play an important role in HD-induced cell injury in human skin.
...
PMID:NAD+ levels and glucose uptake of cultured human epidermal cells exposed to sulfur mustard. 252 91

To analyze a possible involvement of ADP-ribosylation reactions in 3T3-L1 pre-adipocyte differentiation. ADP-ribosyltransferase activities is permeabilized cells as well as endogenous amounts of protein-bound mono- and poly(ADP-ribose) residues were determined. Also, in vivo labeling with [3H]adenosine of ADP-ribose residues linked to high-mobility-group (HMG) proteins was performed. As an additional probe, the effects of ADP-ribosylation inhibitors and non-inhibitory analogs were studied. Basal and total poly(ADP-ribose) polymerase activities markedly increased prior to the appearance of the differentiation marker glycerol-3-phosphate dehydrogenase. Despite these apparent changes in activity, however, neither protein-bound poly(ADP-ribose) residue nor mono(ADP-ribosyl) groups in histones, nor the NAD content, changed significantly under these conditions. Furthermore, although HMG protein-associated [3H]ADP-ribose was reduced in differentiating [3H]adenosine-labeled cells, the data suggest altered precursor pool labeling rather than a specific decrease in ADP-ribosylated HMG proteins. Non-participation of ADP-ribosylation reactions in 3T3-L1 differentiation is further supported by experiments with inhibitors and non-inhibitory analogs. Benzamide at 0.3-3 mM per se without effect on differentiation, was able to induce specific gene expression when combined with insulin (10(-12)-10(-7) M). Similar effects were seen with benzoate as well as with nicotinamide, 3-aminobenzamide and their corresponding acids. The data indicate that benzamide and analogs have profound effects on chromatin functions that are not mediated by ADP-ribosylation reactions.
...
PMID:Differentiation of 3T3-L1 pre-adipocytes induced by inhibitors of poly(ADP-ribose) polymerase and by related noninhibitory acids. 252 99

In HL-60 cells, a human promyelocytic leukemia cell line, the human c-myc gene, designated MYC, is amplified about 16-fold. On differentiation of the HL-60 cells into granulocytes induced by several inhibitors of poly(ADP-ribose) polymerase [NAD+ poly(adenosine diphosphate D-ribose)ADP-D-ribosyltransferase, EC 2.4.2.30] including benzamide, nicotinamide, coumarin, and 4-hydroxyquinazoline or dimethyl sulfoxide, some MYC loss was observed. In contrast, benzoic acid, a noninhibitory analogue of benzamide, did not induce either granulocytic differentiation or loss of MYC. Loss of MYC seems to be associated with granulocytic differentiation because the time course of its loss was similar to that of appearance of nitroblue tetrazolium-positive cells, mature granulocytes, and its loss was not observed on differentiation of HL-60 cells into macrophages induced by phorbol 12-myristate 13-acetate or teleocidin. The loss of MYC is not the reason for the down regulation of MYC expression observed within 1 hr after addition of inducers, since the loss of MYC was not detected by 1-day treatment with inducers.
...
PMID:Loss of the MYC gene amplified in human HL-60 cells after treatment with inhibitors of poly(ADP-ribose) polymerase or with dimethyl sulfoxide. 252 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---