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

We have recently devised an activity-blot procedure permitting the detection, on the same nitrocellulose sheet, of the functional poly(ADP ribose) polymerase (PARP) activity as well as the immunostained active peptide(s) after renaturation of the transferred protein(s). Using this technique we have analyzed the PARP activity in higher and lower eukaryotes directly on crude extracts from cell cultures. This procedure has been extended also to in situ screening of bacterial colonies expressing the PARP enzymatic activity.
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PMID:Detection of poly(ADP ribose) polymerase in crude extracts by activity-blot. 175 Jun 71

The genes for the variant surface glycoprotein (VSG) and procyclin are expressed in a mutually exclusive manner during the life cycle of Trypanosoma brucei and synthesize the most abundant mRNAs specific to the bloodstream and procyclic stages of the parasite, respectively. Genes belonging to the polycistronic transcription unit of the VSG gene (expression site-associated genes [ESAGs]) are uniquely expressed in the bloodstream form, but some members of ESAG families (genes related to ESAGs [GRESAGs]) are independently transcribed outside the VSG gene expression site. We report here that a gene related to ESAG 2, GRESAG 2.1, is present and expressed in a procyclin gene transcription unit (PARP A locus), which is polycistronic. Members of the ESAG 2 family are thus present in the two major differentially stage-regulated transcription units of this parasite.
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PMID:A similar gene is shared by both the variant surface glycoprotein and procyclin gene transcription units of Trypanosoma brucei. 199 4

A protein rich in proline and arginine (proline/arginine-rich protein (PARP] has been isolated from dissociative extracts of bovine nasal and articular cartilage, and its primary structure has been determined. The protein has 218 amino acids, giving a calculated protein Mr of 24,075. In nasal cartilage, this protein is in molar concentrations equivalent to 1/20-1/10 that of the link protein of cartilage proteoglycan aggregates. PARP has also been isolated from bovine articular cartilage, bovine fetal epiphysis, and nonossified human tarsal bones. PARP is similar to various collagen NH2-terminal domains. It is 49% identical to the NH2-terminal end of collagen alpha 1 (XI), 17% identical to the NC4 domain of collagen alpha 1 (IX), and 14% identical to the NC3 domain of collagen alpha 1 (XII). Four cysteines are conserved between type XI collagen and PARP, and these form two disulfide bonds. Two of the cysteines are also conserved between PARP and collagens IX and XII. The homology between the collagens and PARP makes it possible to speculate on the likely disulfide bond pattern in the collagen NH2-terminal domains. It is probable that PARP is a collagen fragment removed during processing in a manner analogous to chondrocalcin (the C-terminal propeptide of type II collagen).
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PMID:Isolation and primary structure of PARP, a 24-kDa proline- and arginine-rich protein from bovine cartilage closely related to the NH2-terminal domain in collagen alpha 1 (XI). 224 97

The variant cell surface glycoprotein (VSG) gene expression sites of the protozoan Trypanosoma brucei are transcribed by an unusual alpha-amanitin resistant RNA polymerase. All other protein coding genes of T.brucei examined to date are transcribed by an alpha-amanitin sensitive RNA polymerase, presumably RNA polymerase II. We now show that transcription of protein coding genes by alpha-amanitin resistant RNA polymerases is not unique to the bloodstream form expressed VSG gene expression sites, but also occurs in insect form trypanosomes, which do not express VSG genes. In insect form trypanosomes transcription of the procyclin or PARP genes is resistant to alpha-amanitin to a degree comparable with that of VSG and ribosomal RNA (rRNA) genes. Comparison of the alpha-amanitin resistantly transcribed PARP and VSG gene families shows that they both produce one of the most abundant mRNAs [1-3% of poly(A)+] and they both encode the major cell surface proteins of their respective life cycle stages. Transcription of a subset of functionally comparable protein coding genes is thus mediated by an RNA polymerase which differs from the regular RNA polymerase II.
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PMID:Alpha-amanitin resistant transcription of protein coding genes in insect and bloodstream form Trypanosoma brucei. 259 73

We report on the individual and combined effects of doxorubicin (DOX) and hyperthermia (HYP) on nucleoid sedimentation and poly (ADP-ribose) polymerase (PARP) activity of L1210 cells. The effects of HYP and DOX on nucleoid sedimentation (increased sedimentation) were similar and correlated with cell viability. No correlation of PARP activity with cell toxicity was evident; the activity of PARP was inhibited by HYP (42 degrees C; 1-3 h) and stimulated by DOX (1-10 microM; 30 min). The HYP-induced inhibition of PARP was actually ameliorated by simultaneous exposure to DOX. Although separate studies have previously suggested that chromatin alterations or the inhibition of PARP might play a role in the effect of HYP, the correlation of nucleoid changes (rather than PARP activity) with cell viability emphasizes the contribution of the former. Furthermore, the results suggest that the nucleoid technique may prove useful in screening potential treatment modalities.
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PMID:Effect of hyperthermia and doxorubicin on nucleoid sedimentation and poly (ADP-ribose) polymerase activity in L1210 cells. 312 5

We have recently described that poly(ADP-ribosyl)-polymerase (PARP) inhibitors rescue U937 cells from apoptosis induced by 1 mM H2O2 oxidative stress; PARP activation leads to a reversible drop in NAD level, which could be blocked by PARP inhibitors (Nos-seri et al., 1994, Exp. Cell Res. 212, 367-373). A phenotypic variant of U937 is characterized by a lower basal NAD level (low NAD, LN U937, as opposed to the original high NAD, HN U937). In LN cells treatment with 1 mM H2O2, although activating PARP, does not lower NAD concentration; puzzlingly, PARP inhibitors increase (instead of decreasing, as occurs in HN cells) the extent of stress-induced apoptosis, leading to a reduced cell survival. NAD concentration could be increased in LN cells by adding nicotinamide (5-and 25-fold increase) to the culture medium. These cells (LN+) behaved as HN U937: oxidative stress induced a NAD drop, the extent of which is dependent on the cells' basal NAD level; moreover, PARP inhibitors could rescue LN+ cells from peroxide-induced apoptosis. H2O2-induced apoptosis is not triggered by NAD depletion, but instead it takes place only when NAD levels have been preserved or have recovered: on HN U937, peroxide doses (5 and 10 mM) which lead to necrosis induce an irreversible NAD drop, whereas apoptosis occurs only at lower doses, where NAD depletion is reversible; on LN cells NAD levels do not drop even upon 10 mM H2O2 treatment, and these cells die only by apoptosis; moreover, in HN cells apoptosis is not detectable until 8 h posttreatment, when NAD levels recover, whereas in LN cells, where NAD is always present, apoptosis begins to take place as early as 3 h after stress.
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PMID:Different basal NAD levels determine opposite effects of poly(ADP-ribosyl)polymerase inhibitors on H2O2-induced apoptosis. 749 46

HN and LN are two phenotypic variants of the U937 monocytic cell line which differ in their basal NAD content; they respond in an opposite way to oxidative stress in the presence of the poly(ADP-ribosyl)polymerase (PARP) inhibitors 3-aminobenzamide (3ABA) and nicotinamide (NA): the inhibitors protect HN cells from stress-induced apoptosis, while they enhance it on LN cells (Coppola et al., 1995, Exp. Cell Res. 221, 462-469). These opposite effects are due to two overlapping and contrasting phenomena occurring in LN cells, as shown by the bi-modal response of stressed LN cells to increasing 3ABA doses. Indeed H2O2-induced apoptosis is enhanced only at high 3ABA concentrations (i.e., sufficient to inhibit also mono-ADP-ribosylations); lower 3ABA concentrations, which specifically inhibit PARP, also protect LN U937 from stress-induced apoptosis. Unlike HN U937, H2O2-induced apoptosis in LN cells is accompanied by cell blebbing. High 3ABA doses strongly enhance blebbing, leading to cellular fragmentation. Blebbing could be blocked by interfering with actin polymerization with cytochalasin B and D: this eliminated the increase in apoptosis due to 3ABA, suggesting that it is indeed the consequence of excess blebbing. This is supported by the unusual finding that in U937 LN stressed in the presence of 3ABA or NA, blebbing, usually a late event in apoptosis, may even precede its onset.
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PMID:The increase in H2O2-induced apoptosis by ADP-ribosylation inhibitors is related to cell blebbing. 749 47

To investigate the origin of DNA repair in rat pleural mesothelial cells (RPMC) exposed to asbestos fibers, poly(ADP-ribose) polymerase (PARP) activity was measured in the asbestos-treated cells. As bleomycin has been shown to activate poly(ADP-ribose) synthesis in several cell systems, the response to bleomycin with regard to PARP assay was first investigated. Bleomycin produced a dose-dependent increase of poly(ADP-ribose) synthesis in RPMC. Likewise both chrysotile and crocidolite fibers produced a concentration-dependent PARP activation indicating that the formation of DNA strand breaks is one type of damage produced by asbestos in RPMC. Enhancement of DNA repair, assessed by the measurement of [3H] methylthymidine incorporation in growth arrested cells, was not detectable in the presence of 3-methoxybenzamide (3-MBA), a PARP inhibitor, confirming a relation between PARP activation and DNA repair. The participation of DNA breakage in asbestos toxicity on RPMC was determined by the colorimetric 3-4(5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. There was no relationship between DNA breakage and cytotoxicity since the use of PARP inhibitors did not change cell viability. These results indicate that asbestos produce DNA damage that is repaired in RPMC.
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PMID:Synthesis of poly(ADP-ribose) in asbestos treated rat pleural mesothelial cells in culture. 750 Sep 78

Poly(ADP-ribose)polymerase (PARP) is a DNA-binding protein that is activated upon induction of DNA breaks and supposed to play a role in DNA repair. To elucidate the effect of overexpression of PARP on the resistance of cells to mutagens, Chinese hamster ovary cells (both the line CHO-9 and the mutagen-hypersensitive derivative 27-1) were transfected with the human PARP cDNA along with pSV2neo. Treatment of the transfected cell population with a high dose of MNNG and selection with G418 gave rise to a significant increase of neo+ clones, as compared to the control transfection with pSV2neo + salmon sperm DNA. The frequency of survivors in these mass culture experiments was lower, however, than after transfection with the bacterial ada gene encoding the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Thus transfection of PARP cDNA in CHO cells is only weakly effective in inducing alkylation resistance. This was confirmed by analyzing the mutagen resistance of individual PARP transfectant clones derived from CHO-9 and 27-1 cells that expressed increased levels of PARP mRNA, protein and PARP activity. These strains were slightly more resistant to the toxic effect of MMS and showed a reduced frequency of MMS-induced chromosomal aberrations. CHO-9-PARP transfectants also gained resistance to UV. From these data we conclude that, in CHO cells, PARP is limiting in handling critical lesions during the repair process and that increase of the amount of PARP protein can elicit some protection against genotoxic effects of mutagens.
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PMID:Effect of transfection of human poly(ADP-ribose)polymerase in Chinese hamster cells on mutagen resistance. 751 39

Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.
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PMID:Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. 756 69


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