Changes in NAD/ADP-ribose metabolism in rectal cancer (original) (raw)
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Tumor Biology, 2014
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ADP-ribosylation of serum proteins: evaluation as a potential tumor marker
Cancer Letters, 1996
Serum samples from cancer patients revealed elevated levels of in vitro ADP-ribosylation through non-enzymic binding of ADP-ribose to free acceptor sites on serum proteins. Low concentrations of serum ADP-ribose caused by high NAD glycohydrolase activity together with elevated rates of ADP-ribose transport into erythrocytes appeared to account for undersaturation of the acceptor sites on serum proteins. ADP-ribosylation of serum proteins was assessed as an indicator of cancer disease, and an attempt was made to determine the correlation of ADP-ribosylation levels with carcinoembryonic antigen (CEA) values. Based on positive test results for all tumor patients and negative test results for all healthy controls, sensitivity and specificity of ADP-ribosylation as a tumor indicator were estimated as 67% and 95%, respectively. A close correlation appeared to exist with CEA (r = 0.67; P < 0.001). Similarly, the changes in the levels of ADP-ribosylation correlated with the changes in the levels of CEA during the clinical course (r = 0.58; P < 0.05).
Molecular and Cellular Biochemistry, 2005
Poly-ADP-ribosylation (PAR) of cellular proteins has been shown to have decisive roles in diverse cellular functions including carcinogenesis. There are indications that metabolic level of poly-ADP-ribosylated cellular proteins might indicate carcinogenesis and, therefore, could be potentially used in cancer screening program. Keeping in mind the limitations of currently available assays of cellular PAR, a new assay is being reported that measures the metabolic level of poly-ADP-ribosylated cellular proteins. The ELISA based slot and Western blot immunoassay used polyclonal antibody against natural, heterogeneous ADP-ribose polymers. It could be successfully employed to qualitatively and quantitatively assay metabolic levels of poly-ADP-ribosylated proteins of spleen and liver tissues of normal mice or mice exposed to dimethylnitrosamine for up to 8 weeks; potentially PAR of cellular proteins could be assayed in any tissue or biopsy. Implications of the results in cancer screening program have been discussed. (Mol Cell Biochem 278: 213–221, 2005)
British journal of cancer, 1998
Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms and the associated activity shown to markedly increase after DNA damage in carcinogen-treated cells. A defective DNA repair has been associated to the aetiology of human cancers. In order to assess the potential role of this enzyme in cellular response to DNA damage by gamma-radiation, we studied the activity of PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP-ribose)polymerase activity by the rate of incorporation of radioactivity from [3H]adenine-NAD+ into acid-insoluble material in permeabilized leucocytes from FAP patients and healthy volunteers. Concomitantly, the intracellular levels of NAD+--the substrate for the PARP--and the reduced counterpart NADH were determined using an enzymatic cycling assay 30 min after [60Co] gamma-ray cells irradiation. Our results demonstrate that a marked stimulation of PARP activity is produced upon radiation of the cells from healthy s...
Poly-ADP-ribosylation - a novel biomarker of human cancers of head & neck, breast, and cervix
2009
Background: Poly-ADP-ribosylation, a reversible post-translational modification of primarily chromosomal proteins, is involved in various cellular and molecular processes including carcinogenesis. ADP-ribose polymer or poly-ADPribose adducts are enzymatically added onto or stripped off the target chromosomal proteins during this metabolic process. Due to this, the chromatin superstructure is reversibly altered, which significantly influences the pattern of gene expression. We hypothesize that a decrease in the concentration of total poly-ADP-ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with the incidence of human cancer. Results: Using a novel immunoprobe assay, we show a statistically significant (P ≤ 0.001) reduction (~42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head & neck (H & N) region (comprising fourteen distinct cancers at different sites), breast and cervix in comparison to healthy controls. Conclusions: These findings imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of significant clinical and epidemiological applications.
ADP-ribosylation of nucleolar proteins in HeLa tumor cells
Journal of Cellular Biochemistry, 1993
ADP-ribosylation reactions in nucleoli of exponentially growing HeLa cells were studied. Isolated nuclei or nucleoli were labeled with 32P-NAD; then the nucleolar proteins were analyzed by 1-dimensional and 2-dimensional polyacrylamide gel electrophoresis (PAGE) and modified proteins were detected by autoradiography. The labeled nucleolar proteins were also chromatographically fractionated on DEAE-cellulose. Electrophoretic analysis of total nucleolar and chromatographically purified proteins revealed that besides nuclear ADP-ribosyltransferase and histones two characteristic nucleolar phosphoproteins n u m a t r i n / B 2 3 and nucleolin/C23 were modified by ADP-ribosylation.
Biochemistry, 1986
A ribonuclease was isolated from serum-free supernatants of the human colon adenocarcinoma cell line HT-29. It was purified by cation-exchange and C 18 reversed-phase high-performance liquid chromatography. The protein is basic, has a molecular weight of -16 000, and has an amino acid composition that is significantly different from that of human pancreatic ribonuclease. The amino terminus is blocked, and the carboxyl-terminal residue is glycine. The catalytic properties of this ribonuclease resemble those of the pancreatic ribonuclezses in numerous respects. Thus, it exhibits a pH optimum of -6 for dinucleotide cleavage and employs a two-step mechanism in which transphosphorylation to a cyclic 2',3'-phosphate is followed by slower hydrolysis to produce a 3'-phosphate. It does not cleave NpN' substrates in which adenosine or guanosine is at the N position and prefers purines at the N' position. Like bovine ribonuclease A, the HT-29-derived ribonuclease is inactivated by reductive methylation or by treatment with iodoacetate at pH 5.5 and is strongly inhibited by the human placental ribonuclease inhibitor. However, in contrast, the tumor enzyme does not cleave C p N bonds at an appreciable rate and prefers poly(uridy1ic acid) as substrate 1000-fold over poly(cytidy1ic acid). It also hydrolyzes cytidine cyclic 2',3'-phosphate at least 100 times more slowly than uridine cyclic 2',3'-phosphate and is inhibited much less strongly by cytidine 2'-monophosphate than by uridine 2'-monophosphate. Other ribonucleases known to prefer poly(uridy1ic acid) were isolated both from human serum and from liver and were compared with the tumor enzyme. The physical, functional, and chromatographic properties of the serum ribonuclease are essentially identical with those of the tumor enzyme. The liver enzymes, however, differ markedly from the HT-29 ribonuclease. The potential utility of the tumor ribonuclease in the diagnosis of cancer is considered.
Possible Model of Liver Carcinogenesis Using Inhibitors of NAD+ ADP Ribosyl Transferase in Rats
Toxicologic Pathology, 1986
The response of cellular NAD+ metabolism to DEN and/or ABA and the carcinogenesis of the liver initiated by DEN and ABA were studied in rats. The liver NAD+ level was depleted by an ip injection of 20 mg or 200 mg/kg body weight of DEN. ABA, administered ip at a dose of 600 mg/kg simultaneously with or 4 hours after DEN, prevented the depletion of NAD' by DEN. These biochemical findings correlated with the changes of conspicuous intranuclear immunofluorescence of poly(ADP-ribose), which were studied by immunohistochemistry. When initiated by 20 mg/kg body weight DEN and 600 mg/kg ABA and then processed to selection pressure, the liver was found to be capable of developing hepatocellular carcinomas with or without PB promotion. These results suggest that the inhibition of poly(ADP-ribosylation) might lead to irreversible initiation of liver carcinogenesis by DEN in rats.
The Eurasia Proceedings of Health, Environment and Life Sciences, 2022
The translation process consists of translation factors and ribosomes. Ribosomal components include ribosomal proteins (RP) and ribosomal RNA. Many RPs are involved in assembling ribosomal particles and or stabilizing important regions of rRNA. Besides their conventional roles, RPs have been reported to exhibit secondary functions that have not yet been fully characterized in other cellular processes such as DNA repair, apoptosis, drug resistance, proliferation, and growth inhibition. Since cancer cells require a large amount of protein, they need ribosomes that work much more efficiently than normal cells. Several tumor suppressors and oncogenic proteins control the progression of cancer cells by regulating ribosome biogenesis and protein synthesis. Interestingly, free RPs also have diverse roles in tumorigenesis or tumor suppression. The physiological link between RPs and cancers has been extensively reviewed and elucidated on several pathways, including their interaction with the...
The Biochemical journal, 1980
Poly(ADP-ribose) polymerase was purified from Ehrlich ascites-tumour cells by two novel methods. Analysis for amino acid composition revealed a high percentage of acidic amino acids or their amides, and of basic amino acids. N-Terminal analysis with dansyl chloride revealed no terminal amino acid, indicating a blocked N-terminal amino group. Analysis by gel electrophoresis of protein treated with 3-bromo-3-methyl-2-[(2-nitrophenylthio)-3H-indole, under conditions where selective cleavage of the polypeptide chain at tryptophan residues is obtained, showed six major peptide bands.