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‣ Histonas de glândulas salivares de Rhynchosciara americana: caracterização e síntese; Histone salivary glands Rhynchosciara americana: characterization and synthesis

Pueyo, Manuel Troyano
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 26/05/1976 Português
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Histonas de glândulas salivares de larvas de Rhynchosciara americana foram extraídas de preparações de núcleos e de cromatina purificada e analisadas por eletroforese em géis de acrilamida. As mobilidades eletroforéticas das histonas ARE e GRR são idênticas e as das histonas KAP, LAR e KAS são levemente diferentes das histonas correspondentes encontradas em vertebrados. É particularmente interessante o comportamento da histona KAP de R. americana, que possui em géis de poliacrilamida mobilidade menor que a histona correspondente do timo de bezerro. Verificou-se, por análise em géis de poliacrilamida-SDS que o peso molecular desta histona é igual a 33.000 daltons, valor maior que o da histona correspondente de timo de bezerro e de outros vertebrados (21.000 a 25.000 daltons). Este resultado coincide com dados obtidos por outros investigadores em Drosophila e Acheta. Isto sugere que o maior peso molecular da histona KAP possa ser uma característica geral dos insetos. Verificou-se, por experimentos da dupla marcação com lísina- 14 C e triptofano-3 H, que a síntese de histonas em glândulas salivares de larvas de R. americana, ocorre no citoplasma em pequenos polirríbossomos contendo 3-4 ribossomos. Estes polirribissomos são particularmente ativos na síntese de histonas por ocasião da abertura máxima do puff B-2 na extremidade proximal da glândula...

‣ Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from sertoli cells

Moreira, Jose Claudio Fonseca; Dal Pizzol, Felipe; Rocha, Adriana Brondani da; Klamt, Fabio; Ribeiro, Nede Carlos; Ferreira, Carlos Jose Sarmento; Bernard, Elena Aida
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Chromatin proteins play a role in the organization and functions of DNA. Covalent modifications of nuclear proteins modulate their interactions with DNA sequences and are probably one of the multiple factors involved in the process of switch on/off transcriptionally active regions of DNA. Histones and high mobility group proteins (HMG) are subject to many covalent modifications that may modulate their capacity to bind to DNA. We investigated the changes induced in the phosphorylation pattern of cultured Wistar rat Sertoli cell histones and high mobility group protein subfamilies exposed to 7 µM retinol for up to 48 h. In each experiment, 6 h before the end of the retinol treatment each culture flask received 370 KBq/ml [32P]-phosphate. The histone and HMGs were isolated as previously described [Moreira et al. Medical Science Research (1994) 22: 783-784]. The total protein obtained by either method was quantified and electrophoresed as described by Spiker [Analytical Biochemistry (1980) 108: 263-265]. The gels were stained with Coomassie brilliant blue R-250 and the stained bands were cut and dissolved in 0.5 ml 30% H2O2 at 60oC for 12 h. The vials were chilled and 5.0 ml scintillation liquid was added. The radioactivity in each vial was determined with a liquid scintillation counter. Retinol treatment significantly changed the pattern of each subfamily of histone and high mobility group proteins.

‣ Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from Sertoli cells

Moreira,J.C.F.; Dal-Pizzol,F.; Rocha,A.B.; Klamt,F.; Ribeiro,N.C.; Ferreira,C.J.S.; Bernard,E.A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2000 Português
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Chromatin proteins play a role in the organization and functions of DNA. Covalent modifications of nuclear proteins modulate their interactions with DNA sequences and are probably one of the multiple factors involved in the process of switch on/off transcriptionally active regions of DNA. Histones and high mobility group proteins (HMG) are subject to many covalent modifications that may modulate their capacity to bind to DNA. We investigated the changes induced in the phosphorylation pattern of cultured Wistar rat Sertoli cell histones and high mobility group protein subfamilies exposed to 7 µM retinol for up to 48 h. In each experiment, 6 h before the end of the retinol treatment each culture flask received 370 KBq/ml [32P]-phosphate. The histone and HMGs were isolated as previously described [Moreira et al. Medical Science Research (1994) 22: 783-784]. The total protein obtained by either method was quantified and electrophoresed as described by Spiker [Analytical Biochemistry (1980) 108: 263-265]. The gels were stained with Coomassie brilliant blue R-250 and the stained bands were cut and dissolved in 0.5 ml 30% H2O2 at 60oC for 12 h. The vials were chilled and 5.0 ml scintillation liquid was added. The radioactivity in each vial was determined with a liquid scintillation counter. Retinol treatment significantly changed the pattern of each subfamily of histone and high mobility group proteins.

‣ Hydrolysis of histones by proteinases.

Harvima, R J; Yabe, K; Fräki, J E; Fukuyama, K; Epstein, W L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/03/1988 Português
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Hydrolysis of histones by proteinases from rat liver, skin and other sources was studied by using a rat thymus histone preparation as the substrate and polyacrylamide-gel electrophoresis and densitometric analysis as the methods to detect histone subtypes and their hydrolysis. The rat mast-cell proteinase I effectively hydrolysed histones except type H4. Thrombin hydrolysed effectively histones H1 and H2A, whereas plasmin hydrolysed all types of histones. Cathepsin D hydrolysed especially histone H2A. Cathepsins B and L hydrolysed all histones more slowly, and cathepsin H hydrolysed them extremely slowly. Epidermal aminoendopeptidase did not hydrolyse histones. Trypsin and chymotrypsin were used as reference enzymes, which hydrolysed all types of histones in very low concentrations. This study suggests that a variety of proteinases could play a role in histone hydrolysis. Hydrolysis of a specific subtype of histones, such as histone H2A at pH 6 by cathepsin D, may be directly involved in regulation of epidermal-cell differentiation.

‣ Phosphorylation of rat thymus histones, its control and the effects thereon of gamma-irradiation.

Fónagy, A; Ord, M G; Stocken, L A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/01/1977 Português
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The phosphate content of rat thymus histones was determined. As expected for a replicating tissue, histones 1 and 2B were more phosphorylated and had higher 32P uptakes than did histones from resting liver nuclei; the other histones all showed 32P uptake, but the phosphate content and uptake of histone 2A was about half that for liver histone 2A. When thymus nuclei were incubated in a slightly hypo-osmotic medium, non-histone proteins and phosphorylated histones were released into solution; this was enhanced if ATP was present in the medium. [gamma-32P]ATP was incorporated into non-histone proteins, including protein P1, and into the ADP-ribosylated form of histone 1; negligible 32P was incprporated into the other, bound, histones. Histones 1 and 2B added to the incubation medium were extensively, and histones 2A and 4 slightly, phosphorylated. Histones released by increasing the ionic strength of the medium were phosphorylated. Added lysozyme and cytochrome c were neither bound nor phosphorylated, but added non-histone protein P1 was phosphorylated, causing other histones to be released from the nuclei, especially histones 2A and 3. The released histones were phosphorylated. gamma-Irradiation decreased 32P uptake into the non-ADP-ribosylated histones 1 and 4; phosphorylation of histone 1 in vitro was unaffected. The importance of non-histone proteins...

‣ Non-histone chromosomal proteins. Evidence for their role in mediating the binding of histones to deoxyribonucleic acid during the cell cycle

Stein, Gary S.; Hunter, Gale; Lavie, Lena
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1974 Português
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By selective dissociation of histones with the ionic detergent sodium deoxycholate, we have demonstrated that these basic chromosomal polypeptides, which are effective inhibitors of transcription, are more tenaciously bound to DNA in mitotic than in S-phase chromatin. Evidence is presented which suggests that cell-cycle-stage-specific non-histone chromosomal proteins can account for such variations in the association of histones with DNA. When chromatin is reconstituted with DNA and histones are pooled from S-phase and mitotic cells and either S-phase or mitotic non-histone chromosomal proteins, a preferential extraction of histones with sodium deoxycholate from chromatin reconstituted with S-phase rather than mitotic non-histone chromosomal proteins is observed. In contrast, the extractability of histones with sodium deoxycholate from nucleohistone complexes reconstituted with DNA pooled from S-phase and mitotic cells and either S-phase or mitotic histones is identical. Since non-histone chromosomal proteins rather than histones are responsible for the differences in chromatin template activity during S-phase and mitosis, we propose that non-histone chromosomal proteins may modify gene expression during the cell cycle by mediating the binding of histones to DNA.

‣ Antigenicity of the Leishmania infantum histones H2B and H4 during canine viscerocutaneous leishmaniasis

Soto, M; Requena, J M; Quijada, L; Perez, M J; Nieto, C G; Guzman, F; Patarroyo, M E; Alonso, C
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /02/1999 Português
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In this study we show that sera from dogs naturally infected with Leishmania infantum contain antibodies that specifically react against the parasite H2B and H4 histones. The Leishmania H2B and the amino-terminal region of the histone H4, expressed as fusion proteins, when confronted with sera from canine viscerocutaneous leishmaniasis (VCL) dogs, were recognized by 63% and 47%, respectively. No reactivity was detected when sera from dogs naturally infected with pathogens other than Leishmania were used. Using a collection of synthetic peptides covering the complete sequence of both proteins, we have determined that the main linear antigenic determinants are located in the amino-terminal domains of these histones. The humoral response against histones H2B and H4 induced during canine leishmaniasis was found to be specific for Leishmania histones, since no cross-reactivity of the VCL sera with mammal histones was observed. Also, a comparative study of the prevalence of antibodies among VCL sera against the four core histones of L. infantum was performed. Although a large heterogeneity of the humoral responses against these proteins was found, histones H2A and H3 seem to be more prevalent immunogens than histones H2B and H4 during canine natural leishmaniasis. The origin of the anti-histone humoral response and its possible implications in the pathogenesis of Leishmania infection are discussed.

‣ Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/06/1989 Português
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An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns (4), have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of 125I- labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated...

‣ CHANGES IN NUCLEAR HISTONES DURING FERTILIZATION, AND EARLY EMBRYONIC DEVELOPMENT IN THE PULMONATE SNAIL, Helix aspersa

Bloch, David P.; Hew, Howard Y. C.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/09/1960 Português
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Calf thymus histories comprising two fractions, one rich in lysine, the other having roughly equal amounts of lysine and arginine, Loligo testes histones rich in arginine, and salmine, are compared with respect to their amino acid compositions, and their staining properties when the proteins are fixed on filter paper. The three types of basic proteins; somatic, arginine-rich spermatid histones, and protamine can be distinguished on the following basis. Somatic and testicular histones stain with fast green or bromphenol blue under the same conditions used for specific staining of histones in tissue preparations. The former histones lose most or all of their stainability after deamination or acetylation. Staining of the arginine-rich testicular histones remains relatively unaffected by this treatment. Protamines do not stain with fast green after treatment with hot trichloracetic acid, but are stained by bromphenol blue or eosin after treatment with picric acid. These methods provide a means for the characterization of nuclear basic proteins in situ. Their application to the early developmental stages of Helix aspersa show the following: After fertilization the protamine of the sperm is lost, and is replaced by faintly basic histones which differ from adult histones in their inability to bind fast green...

‣ Linker Histones Are Mobilized during Infection with Herpes Simplex Virus Type 1▿

Conn, Kristen L.; Hendzel, Michael J.; Schang, Luis M.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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Histones interact with herpes simplex virus type 1 (HSV-1) genomes and localize to replication compartments early during infections. However, HSV-1 genomes do not interact with histones in virions and are deposited in nuclear domains devoid of histones. Moreover, late viral replication compartments are also devoid of histones. The processes whereby histones come to interact with HSV-1 genomes, to be later displaced, remain unknown. However, they would involve the early movement of histones to the domains containing HSV-1 genomes and the later movement away from them. Histones unbind from chromatin, diffuse through the nucleoplasm, and rebind at different sites. Such mobility is upregulated by, for example, phosphorylation or acetylation. We evaluated whether HSV-1 infection modulates histone mobility, using fluorescence recovery after photobleaching. All somatic H1 variants were mobilized to different degrees. H1.2, the most mobilized, was mobilized at 4 h and further so at 7 h after infection, resulting in increases in its “free” pools. H1.2 was mobilized to a “basal” degree under conditions of little to no HSV-1 protein expression. This basal mobilization required nuclear native HSV-1 genomes but was independent of HSV-1 proteins and most likely due to cellular responses. Mobilization above this basal degree...

‣ Histones induce rapid and profound thrombocytopenia in mice

Fuchs, Tobias A.; Bhandari, Ashish A.; Wagner, Denisa D.
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 29/09/2011 Português
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Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage.

‣ Core Histones H2B and H4 Are Mobilized during Infection with Herpes Simplex Virus 1 ▿

Conn, Kristen L.; Hendzel, Michael J.; Schang, Luis M.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2011 Português
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The infecting genomes of herpes simplex virus 1 (HSV-1) are assembled into unstable nucleosomes soon after nuclear entry. The source of the histones that bind to these genomes has yet to be addressed. However, infection inhibits histone synthesis. The histones that bind to HSV-1 genomes are therefore most likely those previously bound in cellular chromatin. In order for preexisting cellular histones to associate with HSV-1 genomes, however, they must first disassociate from cellular chromatin. Consistently, we have shown that linker histones are mobilized during HSV-1 infection. Chromatinization of HSV-1 genomes would also require the association of core histones. We therefore evaluated the mobility of the core histones H2B and H4 as measures of the mobilization of H2A-H2B dimers and the more stable H3-H4 core tetramer. H2B and H4 were mobilized during infection. Their mobilization increased the levels of H2B and H4 in the free pools and decreased the rate of H2B fast chromatin exchange. The histones in the free pools would then be available to bind to HSV-1 genomes. The mobilization of H2B occurred independently from HSV-1 protein expression or DNA replication although expression of HSV-1 immediate-early (IE) or early (E) proteins enhanced it. The mobilization of core histones H2B and H4 supports a model in which the histones that associate with HSV-1 genomes are those that were previously bound in cellular chromatin. Moreover...

‣ N-Acetyl-Heparin Attenuates Acute Lung Injury Caused by Acid Aspiration Mainly by Antagonizing Histones in Mice

Zhang, Yanlin; Zhao, Zanmei; Guan, Li; Mao, Lijun; Li, Shuqiang; Guan, Xiaoxu; Chen, Ming; Guo, Lixia; Ding, Lihua; Cong, Cuicui; Wen, Tao; Zhao, Jinyuan
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 09/05/2014 Português
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Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary...

‣ Rapid Purification of Recombinant Histones

Klinker, Henrike; Haas, Caroline; Harrer, Nadine; Becker, Peter B.; Mueller-Planitz, Felix
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/08/2014 Português
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The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method “rapid histone purification” (RHP) as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

‣ Lung inflammation and damage induced by extracellular histones

Grailer, Jamison J.; Ward, Peter A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Despite decades of research, acute respiratory distress syndrome (ARDS) remains an important clinical challenge due to an incomplete understanding of the pathophysiological mechanisms. No FDA-approved drug therapy currently exists for treatment of humans with ARDS. There is accumulating evidence in rodents and humans suggesting that extracellular histones are strong drivers of inflammation and tissue damage. We recently described an important role for extracellular histones during acute lung injury (ALI) in mice (Bosmann et al., FASEB J. 27:5010–5021 (2013)). Extracellular histones were detected in bronchoalveolar lavage fluids (BALF) from patients with ARDS but not in BALF from non-ARDS patients in intensive care units. Extracellular histones were also detected in BALF from mice during experimental ALI. The presence of extracellular histones was dependent on the two C5a receptors (C5aR and C5L2) and availability of neutrophils. Extracellular histones were highly pro-inflammatory, and caused severe damage to respiratory function. Intratracheal instillation of histones resulted in pro-inflammatory mediator production, epithelial cell damage, disturbances in alveolar-capillary gas exchange, lung consolidation, activation of the coagulation cascade...

‣ Histones Join the Fight against Bacteria Inside Cells

Kolter, Roberto Guillermo
Fonte: eLife Sciences Publications, Ltd Publicador: eLife Sciences Publications, Ltd
Tipo: Artigo de Revista Científica
Português
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Experiments on Drosophila have shown that the histones that are normally bound to lipid droplets inside cells can be released to provide protection against infection.

‣ Isolation of histones and related chromatin structures from spermatozoa nuclei of a dasyurid marsupial, Sminthopsis crassicaudata

Soon, L.; Ausio, J.; Breed, W.; Power, J.; Muller, S.
Fonte: WILEY-LISS Publicador: WILEY-LISS
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
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The spermatozoa of a dasyurid marsupial, Sminthopsis crassicaudata, have two distinct nuclear regions: uniformly electron-dense chromatin (C1) in the interior and fissured chromatin (C2) at the periphery. To investigate whether the differences in morphology are due to incorporation of different packaging proteins, spermatozoa nuclear proteins were characterised by acetic acid-urea polyacrylamide gel electrophoresis (PAGE) and fractionated by reverse-phase high-pressure liquid chromatography (HPLC). The main protein component was protamine I, but a complete histone complement (H1, H2A, H2B, H3, and H4) was also detected. Immunocytochemistry showed localisation of H4, H2B, and H2A histones to the periphery of the nuclei, a region that corresponded to the C2 chromatin. The fissures in the chromatin of this region disappeared following incubation with fish protamines, indicating that the nucleohistone C2 region may be incompletely condensed relative to nucleoprotamines. This observation is consistent with the view that 60% of phosphodiester charges remain negative in nucleohistone DNA, whereas all DNA charges are neutralised in highly compact nucleoprotamines. Treatment of spermatozoa with micrococcal nuclease showed that the C1 chromatin was resistant to digestion...

‣ Binding of chromium(VI) to histones: Implications for chromium(VI)-induced genotoxicity

Levina, A.; Harris, H.; Lay, P.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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The first evidence has been obtained for Cr(VI) (chromate) binding to isolated calf thymus (CT) histones under physiological conditions (pH 7.4, Cl− concentration 152 mM, 310 K). No significant Cr(VI) binding under the same conditions was observed for other extracellular and intracellular proteins, including albumin, apo-transferrin and G-actin, as well as for CT DNA. The mode of Cr(VI) binding to histones was studied by vibrational, electronic and X-ray absorption (X-ray absorption near-edge structure and X-ray absorption fine structure) spectroscopies and molecular mechanics calculations. A proposed binding mechanism includes electrostatic interactions of CrO4 2− with protonated Lys and Arg residues of histones, as well as the formation of hydrogen bonds with the protein backbone. Similarly, Cr(VI) can bind to nuclear localization signals (typically, Lys- and Arg-rich fragments) of other nuclear proteins. Selective binding of Cr(VI) to newly synthesized nuclear proteins (including histones) in the cytoplasm is likely to be responsible for the active transport of Cr(VI) into the nuclei of living cells.; Aviva Levina, Hugh H. Harris and Peter A. Lay; The original publication can be found at www.springerlink.com

‣ Expression des histones déméthylases dans les cellules hématopoïétiques humaines et les leucémies aiguës

Pécheux, Lucie
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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L’importance des modificateurs de la chromatine dans la régulation de l’hématopoïèse et des hémopathies malignes est illustrée par l’histone méthyltransférase Mixed-Lineage Leukemia (MLL) qui est essentielle au maintien des cellules souches hématopoïétiques (CSH) et dont le gène correspondant, MLL, est réarrangé dans plus de 70% des leucémies du nourrisson. Les histones déméthylases (HDM), récemment découvertes, sont aussi impliquées dans le destin des CSH et des hémopathies malignes. Le but de ce projet est d’étudier l’expression des HDM dans les cellules hématopoïétiques normales et leucémiques afin d’identifier de potentiels régulateurs de leur destin. Nous avons réalisé un profil d'expression génique des HDM par qRT-PCR et par séquençage du transcriptome (RNA-seq) dans des cellules de sang de cordon (cellules CD34+ enrichies en CSH et cellules différenciées) et des cellules de leucémie aiguë myéloïde (LAM) avec réarrangement MLL. Les deux techniques montrent une expression différentielle des HDM entre les populations cellulaires. KDM5B et KDM1A sont surexprimés dans les cellules CD34+ par rapport aux cellules différenciées. De plus, KDM4A et PADI2 sont surexprimés dans les cellules leucémiques par rapport aux cellules normales. Des études fonctionnelles permettront de déterminer si la modulation de ces candidats peut être utilisée dans des stratégies d’expansion des CSH...

‣ Analytical strategies for the comprehensive profiling of histone post translational modifications by mass spectrometry and implications for functional analyses

Drogaris, Paul
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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Le long bio-polymère d'ADN est condensé à l’intérieur du noyau des cellules eukaryotes à l'aide de petites protéines appelées histones. En plus de leurs fonctions condensatrices,ces histones sont également la cible de nombreuses modifications post-traductionnelles(MPT), particulièrement au niveau de leur section N-terminale. Ces modifications réversibles font partie d’un code d’histones épi-génétique transmissible qui orchestre et module dynamiquement certains événements impliquant la chromatine, tels l’activation et la désactivation de gènes ainsi que la duplication et la réparation d’ADN. Ces modifications sont impliquées subséquemment dans la signalisation et la progression de cancers, tels que la leucémie. En conséquence, l'élucidation des modifications d’histones est importante pour comprendre leurs fonctions biologiques. Une méthodologie analytique a été mise au point en laboratoire pour isoler, détecter, et quantifier les MPT d’histones en utilisant une approche rapide à deux volets à l’aide d’outils bioinformatiques spécialisés. La méthodologie développée en laboratoire a été validée en utilisant des histones de souche sauvage ainsi que deux types d’histones mutants déficients en enzymes acétyltransferase. Des trois sources d’histones utilisées...