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Extracellular Histones

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https://www.readbyqxmd.com/read/28443467/effect-of-irinotecan-on-hmgb1-mmp9-expression-cell-cycle-and-cell-growth-in-breast-cancer-mcf-7-cells
#1
Saeedeh Keyvani-Ghamsari, Azra Rabbani-Chadegani, Javad Sargolzaei, Maryam Shahhoseini
Irinotecan is a natural alkaloid agent widely used in cancer therapy. High-mobility group protein B1 as a non-histone chromosomal protein plays a fundamental role in gene expression and inflammation. In this study, the effect of irinotecan on high-mobility group protein B1 and MMP9 content, gene expression, cell cycle, and cell growth in human breast cancer cells (MCF-7) was investigated. The cells were exposed to various concentrations of irinotecan and the viability determined by trypan blue exclusion and 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazolium bromide assays...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28441353/matrix-metalloproteinase-gene-activation-resulting-from-disordred-epigenetic-mechanisms-in-rheumatoid-arthritis
#2
REVIEW
Yasuto Araki, Toshihide Mimura
Matrix metalloproteinases (MMPs) are implicated in the degradation of extracellular matrix (ECM). Rheumatoid arthritis (RA) synovial fibroblasts (SFs) produce matrix-degrading enzymes, including MMPs, which facilitate cartilage destruction in the affected joints in RA. Epigenetic mechanisms contribute to change in the chromatin state, resulting in an alteration of gene transcription. Recently, MMP gene activation has been shown to be caused in RASFs by the dysregulation of epigenetic changes, such as histone modifications, DNA methylation, and microRNA (miRNA) signaling...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#3
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28428115/p300-and-c-ebp%C3%AE-regulated-ikk%C3%AE-expression-are-involved-in-thrombin-induced-il-8-cxcl8-expression-in-human-lung-epithelial-cells
#4
Zheng-Wei Huang, Gi-Shih Lien, Chien-Huang Lin, Chun-Ping Jiang, Bing-Chang Chen
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IκB kinase (IKK)/IκBα/nuclear factor (NF)-κB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein β (C/EBPβ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28426042/antibodies-to-h2a-and-h2b-histones-from-the-sera-of-hiv-infected-patients-catalyze-site-specific-degradation-of-these-histones
#5
Svetlana V Baranova, Pavel S Dmitrienok, Nikita V Ivanisenko, Valentina N Buneva, Georgy A Nevinsky
Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Electrophoretically homogeneous IgGs containing no canonical enzymes were isolated from the sera of HIV-infected patients by chromatography on several affinity sorbents including anti-histone Sepharose...
April 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28424695/b-cell-tolerance-to-deiminated-histones-in-balb-c-c57bl-6-and-autoimmune-prone-mouse-strains
#6
Nishant Dwivedi, Annica Hedberg, Ying Yi Zheng, Indira Neeli, Minoru Satoh, Laurence Morel, Ole Petter Rekvig, Marko Radic
Deimination, a posttranslational modification of arginine to citrulline carried out by peptidylarginine deiminases, may compromise tolerance of self-antigens. Patients with connective tissue autoimmunity, particularly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Felty's syndrome, present with autoantibodies to deiminated histones (dH), which thus form a category of antibodies to citrullinated protein antigens (ACPA). In general, ACPA are a sensitive diagnostic for RA and may form in response to the release of nuclear chromatin (DNA plus dH) from granulocytes, usually referred to as neutrophil extracellular traps...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420468/-effect-of-heparin-pretreatment-on-the-level-of-neutrophil-extracellular-traps-of-serum-and-lung-tissue-in-septic-mice
#7
Jing Jiang, Shengtian Mu, Fangxiao Zhang, Yanting Qiao, Yongran Wu, Zhidan Zhang, Xiaochun Ma
OBJECTIVE: To investigate the influence of heparin pretreatment on serum and lung tissue level of neutrophil extracellular traps (NETs) in septic mice model and its molecular mechanism. METHODS: Ninety male C57BL/6J mice were randomly divided into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg LPS in 100 ?L normal saline was intraperitoneally injected) and LPS+heparin group (n = 30, 8 U of heparin in 20 ?L normal saline was subcutaneously injected 30 minutes before the injection of LPS)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28409880/osajin-inhibits-solar-uv-induced-cyclooxygenase-2-expression-through-direct-inhibition-of-rsk2
#8
Jong-Eun Kim, Yong-Seok Heo, Ki Won Lee
Solar ultraviolet light (sUV) has been shown to promote the development of skin disorders including inflammation, photoaging, and skin carcinogenesis. Osajin is the major bioactive isoflavone present in the fruit of Maclura pomifera, commonly referred to as the Osage orange. In this study, we observed that osajin inhibited sUV-induced cyclooxygenase (COX)-2 protein expression in both HaCaT and JB6 cells. COX-2 is a major mediator of skin inflammation. sUV activated the transcription factors nuclear factor- κB and activator protein-1 which, in turn, induces COX-2 expression...
April 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#9
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28374746/intracellular-hmgb1-as-a-novel-tumor-suppressor-of-pancreatic-cancer
#10
Rui Kang, Yangchun Xie, Qiuhong Zhang, Wen Hou, Qingping Jiang, Shan Zhu, Jinbao Liu, Dexing Zeng, Haichao Wang, David L Bartlett, Timothy R Billiar, Herbert J Zeh, Michael T Lotze, Daolin Tang
Pancreatic ductal adenocarcinoma (PDAC) driven by oncogenic K-Ras remains among the most lethal human cancers despite recent advances in modern medicine. The pathogenesis of PDAC is partly attributable to intrinsic chromosome instability and extrinsic inflammation activation. However, the molecular link between these two events in pancreatic tumorigenesis has not yet been fully established. Here, we show that intracellular high mobility group box 1 (HMGB1) remarkably suppresses oncogenic K-Ras-driven pancreatic tumorigenesis by inhibiting chromosome instability-mediated pro-inflammatory nucleosome release...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28374518/neutrophil-extracellular-traps-can-serve-as-platforms-for-processing-and-activation-of-il-1-family-cytokines
#11
Danielle M Clancy, Conor M Henry, Graeme P Sullivan, Seamus J Martin
Activated neutrophils can undergo a mode of regulated cell death, called NETosis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil-derived extracellular traps (NETs) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G. NET-associated factors are thought to enhance the anti-microbial properties of these structures and localisation of anti-microbial molecules on NETs may serve to increase their local concentration...
April 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28373363/re-engineering-the-pancreas-tumor-microenvironment-a-regenerative-program-hacked
#12
EDITORIAL
Gerard I Evan, Nasun Hah, Trevor D Littlewood, Nicole M Sodir, Tania Campos, Michael Downes, Ronald M Evans
The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373289/mir-202-diminishes-tgfbeta-receptors-and-attenuates-tgfbeta1-induced-emt-in-pancreatic-cancer
#13
Hardik Mody, Sau Wai Hung, Rakesh Pathak, Jazmine Griffin, Zobeida Cruz-Monserrate, Rajgopal Govindarajan
Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs (miRs) to regulate endogenous TGFbeta1 levels via miR-663/4787 mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). While DZNep also attenuates exogenous TGFbeta-induced EMT response, the mechanism of this inhibition was unclear...
April 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28371406/in-vitro-generation-of-polysialylated-cervical-mucins-by-bacterial-polysialyltransferases-to-counteract-cytotoxicity-of-extracellular-histones
#14
Sebastian P Galuska, Christina E Galuska, Tharmala Tharmalingam, Kristina Zlatina, Gerlinde Prem, Farzali C O Husejnov, Pauline M Rudd, Willie F Vann, Colm Reid, Justine Vionnet, Mary E Gallagher, Faye A Carrington, Sarah-Louise Hassett, Stephen D Carrington
Neutrophil extracellular traps (NET) are formed against pathogens. However, various diseases are directly linked to this meshwork of DNA. The cytotoxic properties of extracellular histones especially seem to be an important trigger during these diseases. Furthermore, NET accumulation on implants is discussed to result in an impaired efficiency or failure, depending on the category of implant. Interestingly, mucins have been investigated as surface coatings potentially capable of reducing neutrophil adhesion...
March 31, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28370080/evaluation-of-assays-for-quantification-of-dna-in-canine-plasma-as-an-indirect-marker-of-netosis
#15
Stephanie A Smith, Corinne M Lawson, Maureen A McMichael, Katrina Jung, Mauria O'Brien, Ron Achiel
BACKGROUND: Neutrophil extracellular traps (NET), consisting of a filamentous DNA/chromatin-histone scaffold originating from neutrophils are part of the innate immune response, may be released under a variety of inflammatory conditions and are associated with an increased risk for thrombosis. OBJECTIVES: The purpose of this study was to evaluate a SYTOX green fluorescence assay and a histone-DNA complex (hisDNA) ELISA for quantification of NET-related DNA in canine plasma...
April 3, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28359774/trpv4-regulates-insulin-mrna-expression-and-ins-1e-cell-death-via-erk1-2-and-no-dependent-mechanisms
#16
M Billert, M Skrzypski, M Sassek, D Szczepankiewicz, T Wojciechowicz, S Mergler, M Z Strowski, K W Nowak
TRPV4 is a Ca(2+)-permeable, nonselective cation channel. Recently, TRPV4 was implicated in controlling peripheral insulin sensitivity, insulin secretion and apoptosis of pancreatic beta cells. Here, we characterize the role and potential mechanisms of TRPV4 in regulating insulin mRNA expression and cell death in insulin producing INS-1E cells and rat pancreatic islets. TRPV4 protein production was downregulated by siRNA. Intracellular calcium level was measured using Fluo-3 AM. Gene expression was studied by real-time PCR...
March 27, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28359134/circulating-extracellular-dna-cause-or-consequence-of-thrombosis
#17
Miguel Jiménez-Alcázar, Natalie Kim, Tobias A Fuchs
Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism...
March 30, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28350058/neutrophil-extracellular-traps-induce-il-1%C3%AE-production-by-macrophages-in-combination-with-lipopolysaccharide
#18
Zhongshuang Hu, Taisuke Murakami, Hiroshi Tamura, Johannes Reich, Kyoko Kuwahara-Arai, Toshiaki Iba, Yoko Tabe, Isao Nagaoka
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NET‑associated components. In contrast, the components of NETs have been recognized as damage‑associated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure...
January 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28348226/err%C3%AE-induces-h3k9-demethylation-by-lsd1-to-promote-cell-invasion
#19
Julie Carnesecchi, Christelle Forcet, Ling Zhang, Violaine Tribollet, Bruno Barenton, Rafik Boudra, Catherine Cerutti, Isabelle M L Billas, Aurélien A Sérandour, Jason S Carroll, Claude Beaudoin, Jean-Marc Vanacker
Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS)...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28346125/canine-neutrophil-extracellular-traps-enhance-clot-formation-and-delay-lysis
#20
Unity Jeffery, Dana N LeVine
Autoimmune diseases increase the risk of thrombosis. Neutrophil extracellular traps (NETs) are webs of DNA and protein that may mediate thrombosis in autoimmune diseases. Human and murine studies show NET-releasing neutrophils within a thrombus promote its growth, but it is unclear to what extent NET fragments released into circulation during inflammation are prothrombotic. This study hypothesized that canine NETs promote clot formation and impair lysis even in the absence of neutrophils. NETs were prepared from PMA-stimulated neutrophils and added to fibrinogen and thrombin or to recalcified pooled canine platelet-poor plasma, tissue factor, and tissue plasminogen activator...
January 1, 2017: Veterinary Pathology
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