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排序方式: 共有152条查询结果,搜索用时 15 毫秒
1.
Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells.
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T M Chan G Frampton N A Staines P Hobby G J Perry J S Cameron 《Clinical and experimental immunology》1992,88(1):68-74
The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones. 相似文献
2.
Xiao B Jing C Kelly G Walker PA Muskett FW Frenkiel TA Martin SR Sarma K Reinberg D Gamblin SJ Wilson JR 《Genes & development》2005,19(12):1444-1454
Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific. 相似文献
3.
Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone-antihistone immune complexes.
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L F Pereira F M Marco R Boimorto A Caturla A Bustos E G De la Concha J L Subiza 《Clinical and experimental immunology》1994,97(2):175-180
Antibodies recognizing anionic phospholipids have been described in systemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a cardiolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding proteins that are targets of autoantibodies. In this study we have addressed whether this might be the case for histones, a set of highly cationic and widely distributed proteins that react in a well known autoantibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) monoclonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples containing antihistone antibodies often enhances their anticardiolipin reactivity. In addition, we have found that antihistone-producing hybridomas derived from MRL-lpr mice may show anticardiolipin activity due to the presence of histones in the cell culture supernatants with the resultant formation of immune complexes. Taken together, the results suggest a potential role for histones in the anti-cardiolipin activity detected in sera containing antihistone antibodies. These histone-phospholipid interactions should be taken into account when evaluating the pathogenic effects of antihistone antibodies or other autoantibodies reacting with nuclear components (e.g. nucleosomes) containing histones. 相似文献
4.
Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus erythematosus. 总被引:3,自引:0,他引:3
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M Monestier K E Novick E T Karam L Chabanne J C Monier D Rigal 《Clinical and experimental immunology》1995,99(1):37-41
Dogs can develop systemic lupus erythematosus syndromes that are clinically similar to those seen in humans. In contrast, previous observations suggest differences in their autoantibody reactivity patterns against histones and DNA which are components of the nucleosome in chromatin. The objective of this study was to assess comprehensively the levels of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus and control dog sera were determined using IgM- and IgG-specific reagents in an ELISA against a variety of chromatin antigens. When compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosome in lupus dogs. There was no significant increase in any of the IgM specificities tested. Therefore, the reactivity pattern to nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands in contrast with human and murine lupus, where autoantibodies are directed against a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in canine lupus. The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA antibodies are not required for the development of this complication, whereas IgG anti-histone antibodies may be relevant to its pathogenesis. 相似文献
5.
6.
Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression. 相似文献
7.
Vectors based on adenovirus (Ad) are one of the most commonly utilized platforms for gene delivery to cells in molecular biology studies and in gene therapy applications. Ad is also the most popular vector system in human clinical gene therapy trials, largely due to its advantageous characteristics such as high cloning capacity (up to 36 kb), ability to infect a wide variety of cell types and tissues, and relative safety due to it remaining episomal in transduced cells. The latest generation of Ad vectors, helper‑dependent Ad (hdAd), which are devoid of all viral protein coding sequences, can mediate high-level expression of a transgene for years in a variety of species ranging from rodents to non-human primates. Given the importance of histones and chromatin in modulating gene expression within the host cell, it is not surprising that Ad, a nuclear virus, also utilizes these proteins to protect the genome and modulate virus- or vector‑encoded genes. In this review, we will discuss our current understanding of the contribution of chromatin to Ad vector function. 相似文献
8.
J.-H. Lee M. L. Choy L. Ngo S. S. Foster Paul A. Marks 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(33):14639-14644
Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (γH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, γH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death. 相似文献
9.
Azra Rabbani-Chadegani Parisa Paydar Marzieh Amirshenava Asieh Aramvash 《Drug and chemical toxicology》2015,38(2):220-226
Context: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. Objective: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. Materials and methods: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0–160?µg/ml) for 4?h at 23?°C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. Result: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89?KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. Conclusion: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis. 相似文献
10.
Xenotransplantation may be an alternative source of organs for patients with end-stage organ failure, but problems remain to be overcome. Five factors that are problematic are (a) a sustained systemic inflammatory response in the xenograft recipient, (b) thrombotic microangiopathy and disseminated intravascular coagulation, (c) ischemia-reperfusion injury, (d) complement activation, and (e) vascular endothelial cell injury. In xenotransplantation, histones, which are positively charged proteins, are released into the extracellular space from damaged and activated cells, cause cell and tissue damage, and act as danger/damage-associated molecular patterns (DAMPs) that mediate inflammation, coagulation disorders, an immune response, and cytotoxicity. We have previously demonstrated that serum histones increase after pig-to-baboon organ transplantation and infection. Treatment of the recipient with tocilizumab (interleukin-6 receptor blockade) reduces the level of serum histones and C-reactive protein. In this review, the potential role of extracellular histones in xenotransplantation is discussed, and we briefly summarize the relationship between extracellular histones and the inflammatory response, coagulation dysfunction, ischemia-reperfusion injury, the complement system, and vascular endothelial cell injury. 相似文献