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Cytidine Deaminase (cytidine + deaminase)
Kinds of Cytidine Deaminase Selected AbstractsModulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori -Infected Gastric Epithelial CellsHELICOBACTER, Issue 6 2009Syed Faisal Haider Zaidi Abstract Background:, Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori -infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-,B activation by H. pylori and hence, inhibition of NF-,B pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-,B inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-,B inhibitory activity in H. pylori -infected gastric epithelial cells. Materials and Methods:, MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-,B, inhibitors of NF-,B (I,B), and I,B kinase (IKK) complex regulation with or without curcumin. Results:, The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (,10 ,mol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-,B activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (,10 ,mol/L) has suppressed H. pylori -induced NF-,B activation via inhibition of IKK activation and I,B degradation. Conclusion:, Nonbactericidal concentrations of curcumin downregulated H. pylori -induced AID expression in gastric epithelial cells, probably via the inhibition of NF-,B pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori -related gastric carcinogenesis. [source] GANP suppresses DNA recombination, measured by direct-repeat ,-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cellsGENES TO CELLS, Issue 10 2007Mikoto Yoshida Immunoglobulin V-region somatic hypermutation and C-region class-switch recombination are initiated by activation-induced cytidine deaminase (AID) in B-cells. AID-induced DNA damage at the immunoglobulin S-region is known to be repaired by non-homologous end-joining, but repair mechanisms at the V-region remain to be elucidated. In Saccharomyces cerevisiae, DNA homologous recombination is regulated by the expression of Sac3, involved in actin assembly, cell cycle transition and mRNA metabolism. Here, we demonstrate that the Sac3-homologue GANP suppresses DNA recombination in a direct-repeat ,-galactosidase gene construct in mammalian cells. Homozygous ganp gene knockout is embryonic lethal in mice. Embryonic fibroblasts immortalized from hetero-deficient ganp+/, mice showed more DNA recombination than wild-type. In contrast, over-expression of GANP suppressed either spontaneous DNA recombination or that caused by the introduction of aid cDNA into NIH3T3 cells (susceptible to I-sceI restriction enzyme cleavage but not to RAG-mediated immunoglobulin gene recombination). GANP suppresses the DNA recombination not only on the extrachromosomal DNA construct but also on the integrated DNA. The Sac3-homology portion is necessary for the suppressive activity, but the truncated carboxyl terminal MCM3-binding/acetylating region adversely augmented DNA recombination, acting as a dominant negative form. Expression of full-length GANP is critical for suppression of DNA hyper-recombination in mammalian cells. [source] Modulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori -Infected Gastric Epithelial CellsHELICOBACTER, Issue 6 2009Syed Faisal Haider Zaidi Abstract Background:, Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori -infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-,B activation by H. pylori and hence, inhibition of NF-,B pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-,B inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-,B inhibitory activity in H. pylori -infected gastric epithelial cells. Materials and Methods:, MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-,B, inhibitors of NF-,B (I,B), and I,B kinase (IKK) complex regulation with or without curcumin. Results:, The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (,10 ,mol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-,B activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (,10 ,mol/L) has suppressed H. pylori -induced NF-,B activation via inhibition of IKK activation and I,B degradation. Conclusion:, Nonbactericidal concentrations of curcumin downregulated H. pylori -induced AID expression in gastric epithelial cells, probably via the inhibition of NF-,B pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori -related gastric carcinogenesis. [source] Differential expression of activation-induced cytidine deaminase (AID) in nodular lymphocyte-predominant and classical Hodgkin lymphomaTHE JOURNAL OF PATHOLOGY, Issue 5 2005Axel Greiner Abstract Activation-induced cytidine deaminase (AID) is indispensable for class switch recombination and somatic hypermutation of immunoglobulin genes. Expression of AID has been detected in germinal centre centroblasts and in lymphomas derived from germinal centre cells. However, in situ studies of AID expression have until now been hampered by a lack of antibodies suitable for immunohistochemistry. To overcome this problem, an AID-specific monoclonal antibody suitable for immunohistochemical staining of formalin-fixed, paraffin wax-embedded tissue sections has been generated. This antibody was shown to detect AID expression in normal germinal centre B-cells as well as in non-Hodgkin lymphomas with a putative germinal centre origin. Using this antibody, a virtually exclusive cytoplasmic localization of AID in normal and neoplastic B-cells is shown. Employing a combination of immunohistochemistry and AID-specific in situ hybridization, it is demonstrated that AID is consistently expressed in the neoplastic cells of nodular lymphocyte-predominant Hodgkin lymphoma (HLnlp) but only infrequently in classical HL (cHL). This is in keeping with the notion that tumour cells of HLnlp represent transformed germinal centre B-cells showing evidence of somatic hypermutation. AID represents an additional marker useful in the differential diagnosis of HLnlp and cHL. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Substrate and cofactor requirements for RNA editing of chloroplast transcripts in Arabidopsis in vitroTHE PLANT JOURNAL, Issue 1 2005Carla E. Hegeman Summary None of the macromolecular components of the chloroplast RNA editing apparatus has yet been identified. In order to facilitate biochemical purification and characterization of the chloroplast RNA editing apparatus, we have identified conditions suitable for production of chloroplast extracts from the model plant Arabidopsis that are capable of editing exogenous substrates produced by in vitro transcription. A simple poisoned primer extension assay readily quantified editing extent of mutated and wild-type substrates. Maximum editing efficiency typically varied from 10 to 40% with different chloroplast preparations. Substrates carrying as little as 47 nt surrounding the psbE editing site were as efficiently edited as longer substrates. Editing activity was stimulated when either ATP, CTP, or dCTP was provided to the extract, an unusual observation also recently seen with plant mitochondrial editing extracts. Editing was sensitive to a zinc chelator, also a characteristic of the mammalian APOBEC editing enzyme, which is a zinc-dependent cytidine deaminase. [source] AID in reprogramming: Quick and efficientBIOESSAYS, Issue 5 2010Identification of a key enzyme called AID, its activity in DNA demethylation, may help to overcome a pivotal epigenetic barrier in reprogramming somatic cells toward pluripotency Abstract Current methods of reprogramming differentiated cells into induced pluripotent stem cells remain slow and inefficient. In a recent report published online in Nature, Bhutani et al.1 developed a cell fusion strategy, achieving quick and efficient reprogramming toward pluripotency. Using this assay, they identified an immune system protein called activation-induced cytidine deaminase, or AID, which unexpectedly is actually able to "aid" in reprogramming due to its involvement in DNA demethylation that is required for induction of the two key pluripotency genes, Oct4 and Nanog. More recently, Popp et al.2 also reported online in Nature that AID is important for complete cell reprogramming in mammals. Together, these findings provide new insights into how cells are reprogrammed, identify the specific role of AID in cell fate reversal, and advance the field of regenerative medicine. [source] Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein,Barr virus-infected cells in early casesBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2007Klaus Willenbrock Summary Secondary lymphomas occurring in the setting of angioimmunoblastic T-cell lymphoma (AILT) are considered to be rare. Their occurrence has been attributed to Epstein,Barr virus (EBV)-associated lymphoproliferations. A previous study detected a dysregulated hypermutation process in B-cells of AILT. The present study aimed at estimating the frequency of B-cell lymphomas in AILT. By studying the expression of EBV and activation-induced cytidine deaminase (AID) as an indicator of hypermutating cells, we assessed whether B-cell lymphoproliferations in AILT were strictly associated with EBV and whether hypermutation might contribute to lymphomagenesis. Among 161 cases of AILT, diagnosed between 1996 and 2005 at the lymph node registry, Frankfurt, Germany, 19 cases were detected that also had B-cell non-Hodgkin lymphoma (NHL) and two cases had classical Hodgkin lymphoma (HL). EBV was detected in tumour cells of 7/18 NHL and both HL, suggesting that factors other than EBV contribute to lymphomagenesis. AID was expressed in AILT in large cells disseminated in the tissue, implying that the process of somatic hypermutation is ongoing in AILT, although the GC architecture is disrupted. This might be relevant in the development of secondary lymphomas. [source] Antitumor activity of sugar-modified cytosine nucleosidesCANCER SCIENCE, Issue 2 2004Akira Matsuda Nucleoside analogues which show antimetabolic activity in cells have been successfully used in the treatment of various tumors. Nucleosides such as 1-,-D-arabinofuranosylcytosine (araC), 6-mercaptopurine, fludarabine and cladribine play an important role in the treatment of leukemias, while gemcitabine, 5-fluorouracil and its prodrugs are used extensively in the treatment of many types of solid tumors. All of these compounds are metabolized similarly to endogenous nucleosides and nucleotides. Active metabolites interfere with the de novo synthesis of nucleosides and nucleotides or inhibit the DNA chain elongation after being incorporated into the DNA strand as terminators. Furthermore, nucleoside antimetabolites incorporated into the DNA strand induce strand-breaks and finally cause apoptosis. Nucleoside antimetabolites target one or more specific enzyme(s). The mode of inhibitory action on the target enzyme is not always similar even among nucleoside antimetabolites which have the same nucleoside base, such as araC and gemcitabine. Although both nucleosides are phosphorylated by deoxycytidine kinase and are also good substrates of cytidine deaminase, only gemcitabine shows antitumor activity against solid tumors. This suggests that differences in the pharmacological activity of these nucleoside antimetabolites may reflect different modes of action on target molecules. The design, in vitro cytotoxicity, in vivo antitumor activity, metabolism and mechanism of action of sugar-modified cytosine nucleosides, such as (2,S)-2,-deoxy-2,-C-methylcytidine (SMDC), 1-(2-deoxy-2-methylene-,-D-erythro-pentofuranosyl)cytosine (DMDC), 1-(2-C-cyano-2-deoxy-1-,-D-arabino-pentofuranosyl)cytosine (CNDAC) and 1-(3-C-ethynyl-,-D-ribo-pentofuranosyl)cytosine (ECyd), developed by our groups, are discussed here. [source] Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication,HEPATOLOGY, Issue 6 2006Marianne Bonvin Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-,) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3BL inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3BS and A3C had no effect. A3BL and A3BS were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. Moreover, A3G, A3F, and A3BL, but not A3BS, induced extensive G-to-A hypermutations in a fraction of the replicated HBV genomes. In conclusion, the editing enzymes A3BL, A3F, and most markedly A3G, which are expressed in liver and up-regulated by IFN-, in hepatocytes, are candidates to contribute to the noncytolytic clearance of HBV. (HEPATOLOGY 2006;43:1364,1374.) [source] | |||||||||||||