Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.143 (poly(ADP-ribose) glycohydrolase)
 208 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proflavine, ethacridine (2-ethoxy-6,9-acridine diamine), ellipticine, daunomycin and Tilorone R10,556 DA (2,7-bis(piperidinobutyryl)-9H-fluoren-9-one) inhibit poly(ADP-ribose) glycohydrolase activity. The Ki values for proflavine and Tilorone R10,556 DA are 36 microM and 7.3 microM, respectively. The inhibition by intercalators is relieved by DNA but not by DNA-histone complexes. On the contrary, DNA-histone complexes increase the inhibition of some intercalators. Ethidium bromide is not inhibitory by itself. However, in the presence of DNA-histone complexes it strongly inhibits the enzyme activity. m-AMSA (4'-(9-acridinylamino)methanesulphon-m-anisidide) and chloroquine have no effect on the enzyme activity, even in the presence of DNA-histone complexes.
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PMID:Effect of DNA intercalators on poly(ADP-ribose) glycohydrolase activity. 383 53

Poly(ADP-ribose) synthetase was identified as the main acceptor of this polymer produced in isolated nuclei of rat liver. When the nuclei were incubated with [32P]NAD at a limited concentration (2.4 microM) and for a brief period (10 s), a protein with Mr = 110,000 was predominantly poly(ADP-ribosyl)ated, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The modification of this protein increased upon longer incubations or at higher NAD concentrations, and induced a marked increase in the apparent molecular weight. A comparison with poly(ADP-ribose) synthetase (Mr = 110,000) of rat liver under various conditions suggested that the increase in the molecular weight of the acceptor resembled that of the synthetase undergoing multiple auto-poly(ADP-ribosyl)ation. This interpretation was further supported by the following observations: 1) [32P]poly(ADP-ribose) attached to the acceptor co-eluted with the synthetase activity from a hydroxyapatite column; 2) the [32P]poly(ADP-ribose).acceptor complex isolated on the column was converted to a very large complex by further incubation with NAD; and 3) a group of large poly(ADP-ribose).acceptor complexes were reduced to a single molecular species with Mr = 110,000 by extensive digestion with poly(ADP-ribose) glycohydrolase. These findings altogether suggested that poly(ADP-ribose) synthesized in isolated nuclei was principally bound to the synthetase itself.
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PMID:Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei. 626 Jul 86

Previously it had been shown that poly(ADP-ribose) polymerase requires DNA for its activity and that this enzyme is auto-poly(ADP-ribosyl)ated. The studies reported here indicate that this self-modification inhibits the enzyme and decreases its affinity for DNA, as shown by sucrose gradient density centrifugation. The coupling of poly(ADP-ribose) polymerase with poly(ADP-ribose) glycohydrolase reactivates the polymerase by degrading poly(ADP-ribose) and restoring the polymerase-DNA complex. The assay of polymerase in the presence of glyco-hydrolase was made possible by use of a double-label assay involving release of 14C-labelled nicotinamide and the incorporation of 3H-labelled ADP-ribose from NAD+. These results provide the basis for a shuttle mechanism in which the polymerase can be moved on and off DNA by the action of these two enzymes. Mg2+ and histone H1 appear to activate the polymerase by increasing the affinity of the polymerase for DNA.
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PMID:A shuttle mechanism for DNA-protein interactions. The regulation of poly(ADP-ribose) polymerase. 629 17

Poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase have been detected in chromatin extracts from the dinoflagellate Crypthecodinium cohnii. Poly(ADP-ribose) glycohydrolase was detected by the liberation of ADP-ribose from poly(ADP-ribose). Poly(ADP-ribose) polymerase was proved by (a) demonstration of phosphoribosyl-AMP in the phosphodiesterase digest of the reaction product, (b) demonstration of ADP-ribose oligomers by fractionation of the reaction product on DEAE-Sephadex. The (ADP-ribose)-protein transfer is dependent on DNA; it is inhibited by nicotinamide, thymidine, theophylline and benzamide. The protein-(ADP-ribose bond is susceptible to 0.1 M NaOH (70%) and 0.4 M NH2OH (33%). Dinoflagellates, nucleated protists, are unique in that their chromatin lacks histones and shows a conformation like bacterial chromatin [Loeblich, A. R., III (1976) J. Protozool. 23, 13--28]; poly(ADP-ribose) polymerase, however, has been found only in eucaryotes. Thus our results suggest that histones were not relevant to the establishment of poly(ADP-ribose) during evolution.
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PMID:Presence of poly (ADP-ribose) polymerase and poly (ADP-ribose) glycohydrolase in the dinoflagellate Crypthecodinium cohnii. 632 Nov 75

The activities of three principal enzymes engaged in the biosynthesis and degradation of poly(adenosine diphosphate-ribose) [poly(ADP-ribose)] were examined in cell nuclei isolated from adenomatous polyps (tubular adenomas of familial polyposis coli, villous adenoma, and tubulovillous adenoma), cancers, and normal mucosa of human colon. The activities of poly(ADP-ribose) synthetase in adenomatous polyps [161 +/- 46 (S.E.) pmol/min/mg DNA] and cancers (114 +/- 32 pmol/min/mg DNA) were, on an average, about 3 and 2 times, respectively, higher than those in normal mucosa (52 +/- 24 pmol/min/mg DNA); the difference was statistically significant (p less than 0.001). The activity of poly(ADP-ribose) glycohydrolase was also significantly high in adenomatous polyps (13.0 +/- 3.4 nmol/min/mg DNA), but not in cancers (10.1 +/- 2.5 nmol/min/mg DNA), compared with normal mucosa (5.2 +/- 1.4 nmol/min/mg DNA) (p less than 0.001). The activity of ADP-ribosyl protein lyase, in contrast, was lower in adenomatous polyps (152 +/- 40 pmol/min/mg DNA) than in normal mucosa (345 +/- 111 pmol/min/mg DNA) and cancers (288 +/- 80 pmol/min/mg DNA) (p less than 0.001). Analyses of reaction products with snake venom phosphodiesterase digestion revealed that poly(ADP-ribose) synthesized in nuclei of normal mucosa, adenomatous polyps, and cancers had the average chain lengths of 2.9, 1.7, and 9.7 ADP-ribose units, respectively. Based upon these values and total amounts of ADP-ribose incorporated, the amount of poly(ADP-ribose) synthesized per mg DNA in 30 min was calculated as 308, 1510, and 106 pmol in the above three types of colon tissues, respectively. These results suggested that a larger amount of monomers and short oligomers of ADP-ribose was synthesized in adenomatous polyps, while a smaller number of longer polymers was produced in cancers as compared with normal mucosa. Immunohistochemical analysis of these tissues using anti-poly(ADP-ribose) antibody supported this view.
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PMID:Aberration of poly(adenosine diphosphate-ribose) metabolism in human colon adenomatous polyps and cancers. 640 58

Poly(ADP-ribose) synthetic activity in isolated nucleoli from rapidly growing mouse ascites tumor cells and ADP-ribosylation of the nucleolar proteins in vitro were studied. The specific activity of the synthesis in the nucleoli was significantly higher than that in the chromatin. The optimum magnesium and NAD+ concentrations, and the effect of RNase treatment on the reaction in the nucleoli were also distinctly different from those in the chromatin. Hydrolysis of the reaction product of the nucleoli with snake venom phosphodiesterase and with calf thymus poly(ADP-ribose) glycohydrolase yielded 5'-AMP and 2'-(5"-phosphoribosyl))5'-AMP, and ADP-ribose, respectively. The average chain length of the polymer formed in the nucleoli was found to be about 4 as a whole, but the distribution was heterogenous, from 1.2 to over 12. Analysis of ADP-ribosylated proteins in the nucleoli by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed that several non-histone proteins with molecular weights of over 100,000 were highly ADP-ribosylated compared with other proteins including histones. This pattern was also different from that of the chromatin. These experimental results demonstrate that the nucleoli are independent from the chromatin as regards poly(ADP-ribose) synthesis in vitro.
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PMID:Poly(ADP-ribose) synthesis in nucleoli and ADP-ribosylation of nucleolar proteins in mouse ascites tumor cells in vitro. 728 63

Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), a nitrogen-in-the-ring analog of ADP-ribose, was recently shown to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Analysis of the inhibition kinetics of the hydrolase by ADP-HPD using the method of Lineweaver and Burk yields a noncompetitive double-reciprocal plot. Both the intercept (1/V) versus [inhibitor] replot and the slope (Km/V) versus [inhibitor] replot are hyperbolic, indicating partial noncompetitive inhibition. Inhibitor dissociation constants Kii = 52 nM and Kis = 80 nM were determined for ADP-HPD by analysis of the intercept versus [inhibitor] and slope versus [inhibitor] replots. These results show that although ADP-HPD is extremely potent in inhibiting poly(ADP-ribose) glycohydrolase, its effectiveness is limited by its partial inhibition. ADP-HPD was significantly less potent as an inhibitor of the NAD glycohydrolase from Bungarus fasciatus venom. Analysis of the inhibition kinetics using the Lineweaver and Burk method indicated that ADP-HPD was a linear-competitive inhibitor of the NAD glycohydrolase with a Ki of 94 microM. The results indicate that at low concentration ADP-HPD will be a selective inhibitor of poly(ADP-ribose) glycohydrolase; however, complete inactivation of the activity will be difficult to obtain.
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PMID:Mechanism of inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol. 747 61

Poly(ADP-ribose) metabolism plays an important role in numerous DNA-related functions. This homopolymer is synthesized by poly(ADP-ribose) polymerase and is degraded mainly by the poly(ADP-ribose) glycohydrolase. The activities of these two enzymes in the nucleus are closely coordinated. To better understand the interactions between these enzymes, we designed an in vitro system in which both enzymes are present at the same time. In this work, we report a model describing the synthesis and degradation of the poly(ADP-ribose) in turnover conditions. Because the half-life of the polymer in the cell is close to 1 min, we studied the very early kinetic interactions of these two enzymes.
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PMID:Equilibrium model in an in vitro poly(ADP-ribose) turnover system. 749 64

We describe here the latest observations on poly(ADP-ribose) glycohydrolase. There is now extensive evidence that this nuclear enzyme is an endo-exoglycosidase which has a key role to perform in the removal of polymers which interact with proteins through covalent and non-covalent interactions. Also, we have developed a zymogram which will permit the isolation of the various isoforms of the glycohydrolase and the eventual cloning of this enzyme. Finally, we have evidence that very short oligomers and even monomers of ADP-ribose covalently bound to proteins can be removed by poly(ADP-ribose) glycohydrolase.
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PMID:Biochemical properties and function of poly(ADP-ribose) glycohydrolase. 757 25

Poly(ADP-ribose) polymerase, a nuclear enzyme, is suggested to be involved in apoptotic cell death. It is also known that apoptotic cell death following HIV-1 infection is the most important feature of AIDS pathogenesis. Thus, to evaluate the relations between the enzyme and HIV-1 infection, we examined the enzyme activity of several subclones of human promonocytic cell line U937, which showed different susceptibility to HIV-1 infection. The nuclear extracts of two "high type clones" (possessing high susceptibility to HIV-1 infection) contained approximately 4 to 7-fold less enzyme than two low type clones when assayed under a full activation of enzyme. Parent clone, possessing an intermediate susceptibility to HIV-1, showed an intermediate enzyme level, suggesting that low level of this enzyme in cells is important for an effective infection of HIV-1. Furthermore, when these U937 subclones persistently infected with HIV-1 were examined, a dramatic decrease of the enzyme activity, reaching 2 to 16% of uninfected cells, was observed in all of these clones. The levels of poly(ADP-ribose) glycohydrolase in these clones were relativity unchanged. Activity gel analysis and immunoblotting of the enzyme in the clones revealed that the low enzyme activities observed in uninfected "high type clones" and all HIV-1-infected clones were due to a marked decrease of the enzyme protein itself. All of these results suggest that HIV-1 infection involves some mechanism to downregulate cellular poly(ADP-ribose) polymerase and that a lower level of the enzyme may be essential for an effective production of the virus and/or for a stable virus/host interaction.
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PMID:Poly(ADP-ribose) polymerase activity in various U937 cell subclones with different susceptibility to HIV-1 infection: its dramatic decrease following persistent virus infection. 763 31


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