Disease relevance of CCRIS 3925

• Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B [1].
• No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide [2].
• Here we demonstrate that 3-aminobenzamide (and several other, chemically distinct, inhibitors of PARS activity) reduces the infarct size caused by ischemia and reperfusion of the heart or skeletal muscle of the rabbit [3].
• 3-Aminobenzamide (10 mg/kg IP) preserved the ex vivo contractility of aortas obtained from endotoxic rats and improved survival in lethal murine endotoxic shock [4].
• Nuclease attack may play a role in the increased cellular toxicity attendant on growth in 3-aminobenzamide [5].

Psychiatry related information on CCRIS 3925

• To increase knowledge about the defense mechanisms of pancreatic beta-cells exposed to acute injury, the patterns of protection exerted by 3-aminobenzamide and nicotinamide against the effects of streptozotocin have been studied in vivo and in vitro [6].

High impact information on CCRIS 3925

• An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity [7].
• This effect could be reversed with the PARP inhibitor 3-aminobenzamide and did not occur in cells overexpressing a PARP-dead mutant of tankyrase 1 [8].
• However, if the medium was supplemented with 3-aminobenzamide or nicotinamide, two compounds that inhibit poly(ADP-ribose) formation, cellular NAD+ and ATP pools were preserved, and the lymphocytes responded vigorously to a mitogenic challenge [9].
• Inhibition by IFN-gamma (100-300 U/ml after 5-6 d) was, however, completely prevented by addition of two inhibitors of adenosine diphosphate-ribosyl transferase (ADP-RT), 3-aminobenzamide or nicotinamide [10].
• This down-regulation effect of PARP-1 depended on NACP-Rep1 being present in the construct and was abrogated by inhibiting PARP-1's catalytic activity with 3-aminobenzamide [11].

Chemical compound and disease context of CCRIS 3925

• Protection against myocardial ischemia and reperfusion injury by 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase [12].
• To identify whether PARP activation plays a role in peroxynitrite-induced oligodendrocyte toxicity, we examined the effects of the PARP inhibitors 3-aminobenzamide (3AB) and 5-iodo-6-amino-1,2-benzopyrone (INH(2)BP) on mitochondrial function and cell death in oligodendrocytes [13].
• In vivo administration of the PARS inhibitor 3-aminobenzamide (10 mg/kg i.v.) to rats subjected to myocardial ischemia and reperfusion, reduced myocardial infarct size and blunted the increase in plasma creatine phosphokinase activity and myeloperoxidase activity in infarcted hearts [12].
• In addition, the hypoxia/reoxygenation injury was attenuated by poly(ADP-ribose)synthetase inhibitors such as banzamide, 3-aminobenzamide and 1,5-isoquinolinediol [14].
• We have analyzed the effect of the poly(ADP-ribose) synthesis inhibitor 3 aminobenzamide (3AB) on de novo and methyl methanesulfonate (MMS) and gamma irradiation enhancement of viral transformation of a cloned rat embryo fibroblast cell line, CREF, by a cold-sensitive host-range mutant of type 5 adenovirus, H5hr1 [15].

Biological context of CCRIS 3925

• The poly(ADP)-ribose synthetase inhibitor 3-aminobenzamide suppressed IFN-alpha/beta-induced 2',5'-OAS gene expression [16].
• Accumulation of 10-kilobase DNA replication intermediates in cells treated with 3-aminobenzamide [17].
• Addition of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, with the DNase I completely abolished the fluorescence in the nuclei of synchronously and randomly growing HeLa cells, except in M-phase nuclei [18].
• A 2-minute exposure to 100 micromol/L H2O2 decreased intracellular ATP levels by approximately 40%; this was prevented by 3-aminobenzamide and nicotinamide (1 mmol/L each), inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase [19].
• However, the treatment of HmdUrd-containing cells with 3-aminobenzamide caused extensive cell death [20].

Anatomical context of CCRIS 3925

• Similarly, in cultured human endothelial cells, oxidative- or cytokine-dependent expression of P-selectin and ICAM-1 is reduced by pharmacological inhibition of PARS by 3-aminobenzamide [21].
• As shown by the patch-clamp technique, 11,12-EET stimulated the activation of the K(+) channels in the smooth muscle cells, and this activation was completely blocked by novobiocin, vitamin K(1), 3-aminobenzamide, and m-iodobenzylguanidine, inhibitors of endogenous mono-ADP-ribosyltransferases [22].
• Administration of 3-aminobenzamide also reduced PARS activation and vascular hyporeactivity of rat thoracic aortas exposed to ONOO- (300 mumol/L to 1.5 mmol/L) in vitro [4].
• Effect of 3-aminobenzamide on the rate of ligation during repair of alkylated DNA in human fibroblasts [23].
• Similar to our CPT-resistant cell lines, the resistance of transfected cell lines was reversed by treatment with 3-aminobenzamide [24].

Associations of CCRIS 3925 with other chemical compounds

• The Km, pH optimum, optimal reaction temperature, and inhibition by 3-aminobenzamide and 3-methoxybenzamide were found to be similar for the recombinant and the human enzymes [25].
• The PARS inhibitors 3-aminobenzamide (1 mmol/L), nicotinamide (1 mmol/L), and PD 128763 (100 mumol/L) inhibited the reduction in cellular NAD+ and ATP and the suppression of mitochondrial respiration in response to LPS and IFN-gamma stimulation [4].
• Our results have shown that 1) when transfected in control cells, the plasmid maintains its characteristic unmethylated pattern, whereas this pattern is lost when the plasmid is transfected in cells treated with 3-aminobenzamide; and 2) the presence of new methyl groups on plasmid DNA is paralleled by a decrease of CAT reporter gene expression [26].
• This balance appears to be regulated at the ligation step by adenosine diphosphate ribosylation, which is rapidly altered by addition or removal of 3-aminobenzamide [23].
• Instead, by inhibiting polyadenosine diphosphoribose polymerase or by other side effects, 3-aminobenzamide appears to elicit random nuclease attack of cellular DNA [5].

Gene context of CCRIS 3925

• Expression of UVDE in XRCC1-defective EM9, a Chinese hamster ovary cell line, greatly sensitizes the host cells to UV, and addition of 3-aminobenzamide results in almost no further sensitization of the cells to UV [27].
• However, the presence of 3AB but not its analog suppressed radiation-induced accumulation of wtp53 and the expression of WAF1 and MDM2 [28].
• Treatment with the PARP-1 inhibitors 3-aminobenzamide or 4-amino-1,8-naphthalimide during the insult improved HBMEC viability at 24 h after insult, and resulted in dose-dependent reductions in TUNEL-positivity at 16 h after insult, but not if these treatments were delayed by 4 h [29].
• We demonstrated that specific inhibition of poly(ADP-ribose) polymerase activity via 3-aminobenzamide (3ABA) or NAD+ deprivation prevents FGF2-mediated uPA mRNA over-expression and cell-associated plasminogen activator (PA) production in GM7373 endothelial cell line [30].
• The aim of the present study was to examine the effects of 3-aminobenzamide (3-AB), an inhibitor of PARP activity, in the development of acute pancreatitis caused by cerulein in mice [31].

Analytical, diagnostic and therapeutic context of CCRIS 3925

• We have investigated the ligation of 10-kb DNA replication intermediates to high molecular weight DNA, using the drug 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthetase [17].
• The purification procedure involves affinity chromatography with 3-aminobenzamide as the ligand [32].
• Ninety percent depancreatized rats received daily intraperitoneal injection of 0.5 g/kg nicotinamide and 0.05 g/kg 3-aminobenzamide, potent inhibitors of islet poly(ADP-ribose) synthetase [33].
• Northern blotting analysis showed that 3AB inhibited the gamma-ray-induced WAF1 gene expression [28].
• The spectrum of mutations observed after electroporation of PvuII (which produces blunt-end double-strand breaks) or PvuI (which produces cohesive-end double-strand breaks) was similar in untreated and 3-aminobenzamide-treated cells [34].

References