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Extracellular Histones

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https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#1
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#2
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#3
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29759420/lysyl-oxidase-like-2-contributes-to-renal-fibrosis-in-col4%C3%AE-3-alport-mice
#4
Dominic Cosgrove, Brianna Dufek, Daniel T Meehan, Duane Delimont, Michael Hartnett, Gina Samuelson, Michael Anne Gratton, Grady Phillips, Deidre A MacKenna, Gretchen Bain
Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Here we determine whether LOXL2 influences kidney disease in COL4A3 (-/-) Alport mice. These mice were treated with a small molecule inhibitor selective for LOXL2 or with vehicle and assessed for glomerular sclerosis and fibrosis, albuminuria, blood urea nitrogen, lifespan, pro-fibrotic gene expression and ultrastructure of the glomerular basement membrane...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29752310/extracellular-histones-inhibit-complement-activation-through-interacting-with-complement-component-4
#5
Yasir Qaddoori, Simon T Abrams, Paul Mould, Yasir Alhamdi, Stephen E Christmas, Guozheng Wang, Cheng-Hock Toh
Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with KD around 1 nM...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29750994/regulation-of-cardiac-fibroblast-mmp2-gene-expression-by-scleraxis
#6
Raghu S Nagalingam, Hamza A Safi, Danah S Al-Hattab, Rushita A Bagchi, Natalie M Landry, Ian M C Dixon, Jeffrey T Wigle, Michael P Czubryt
Remodeling of the cardiac extracellular matrix is responsible for a number of the detrimental effects on heart function that arise secondary to hypertension, diabetes and myocardial infarction. This remodeling consists both of an increase in new matrix protein synthesis, and an increase in the expression of matrix metalloproteinases (MMPs) that degrade existing matrix structures. Previous studies utilizing knockout mice have demonstrated clearly that MMP2 plays a pathogenic role during matrix remodeling, thus it is important to understand the mechanisms that regulate MMP2 gene expression...
May 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29749542/the-hdac6-inhibitor-acy%C3%A2-1215-enhances-the-anticancer-activity-of-oxaliplatin-in-colorectal-cancer-cells
#7
Dong Hoon Lee, Hye-Rim Won, Hyun-Wook Ryu, Jung Min Han, So Hee Kwon
ACY‑1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY‑1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY‑1215 and anticancer agents in hematological cancers could occur in solid tumors...
May 11, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29739865/2-chlorofatty-acids-lipid-mediators-of-neutrophil-extracellular-trap-formation
#8
Elisa N D Palladino, Lalage A Katunga, Grant R Kolar, David A Ford
Neutrophils form neutrophil extracellular traps (NETs), which have been implicated in microcirculatory plugging. NET formation (NETosis) involves the fusion of granule and nuclear contents, which are then released in the extracellular space. Myeloperoxidase (MPO) plays a major role in NETosis leading to the dissociation of DNA from histones. During neutrophil activation, MPO is released and activated to convert hydrogen peroxide and chloride to hypochlorous acid (HOCl). HOCl targets plasmalogens leading to the production of the chlorinated lipids, 2-chlorofatty aldehyde (2-ClFALD) and 2-chlorofatty acid (2-ClFA)...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29736733/paeonol-reduces-the-nucleocytoplasmic-transportation-of-hmgb1-by-upregulating-hdac3-in-lps-induced-raw264-7-cells
#9
Qin Xu, Xia Liu, Liyan Mei, Quan Wen, Jing Chen, Jifei Miao, Hang Lei, Huina Huang, Dongfeng Chen, Shaohui Du, Aijun Liu, Saixia Zhang, Jianhong Zhou, Rudong Deng, Yiwei Li, Chun Li, Hui Li
Extracellular high mobility group box 1 (HMGB1) is a lethal pro-inflammatory mediator in endotoxin shock. Hyperacetylation of HMGB1, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), changes its subcellular localization and secretion to the extracellular matrix. Paeonol (2'-hydroxy-4'-methoxyacetophenone), one of the main active components of Paeonia suffruticosa, exerts anti-inflammatory effects. Our previous study demonstrated that Paeonol inhibited the relocation and secretion of HMGB1 in lipopolysaccharide (LPS)-activated RAW264...
May 7, 2018: Inflammation
https://www.readbyqxmd.com/read/29717278/role-of-obesity-in-the-release-of-extracellular-nucleosomes-in-acute-pancreatitis-a-clinical-and-experimental-study
#10
Salvador Pérez, Isabela Finamor, Pablo Martí-Andrés, Javier Pereda, Ana Campos, Rosário Domingues, Fawaz Haj, Luis Sabater, Enrique de-Madaria, Juan Sastre
BACKGROUND/OBJECTIVES: A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats. METHODS: DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29706035/silencing-histone-deacetylase-7-alleviates-transforming-growth-factor-%C3%AE-1-induced-profibrotic-responses-in-fibroblasts-derived-from-peyronie-s-plaque
#11
Dong Hyuk Kang, Guo Nan Yin, Min Ji Choi, Kang Moon Song, Kalyan Ghatak, Nguyen Nhat Minh, Mi Hye Kwon, Do Hwan Seong, Ji Kan Ryu, Jun Kyu Suh
PURPOSE: Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque...
May 2018: World Journal of Men's Health
https://www.readbyqxmd.com/read/29703474/platelets-nets-and-cancer
#12
Jessica Cedervall, Anahita Hamidi, Anna-Karin Olsson
In addition to the central role of platelets in hemostasis, they contribute to pathological conditions such as inflammation and tumor progression. Aberrant expression and/or exposure of pro-coagulant factors in the tumor microenvironment induce platelet activation and subsequent release of growth factors from platelet granules. Cancer patients are commonly affected by thrombotic events, as a result of tumor-induced platelet activation. A novel player potentially contributing to cancer-associated thrombosis is the formation of neutrophil extracellular traps (NETs)...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29694837/planarian-flatworms-as-a-new-model-system-for-understanding-epigenetic-regulation-of-stem-cell-pluripotency-and-differentiation
#13
REVIEW
Anish Dattani, Divya Sridhar, Aziz Aboobaker
Planarian flatworms possess pluripotent stem cells (neoblasts) that are able to differentiate into all cell types that constitute the adult body plan. Consequently, planarians possess remarkable regenerative capabilities. Transcriptomic studies have revealed that gene expression is coordinated to maintain neoblast pluripotency, and ensure correct lineage specification during differentiation. But as yet they have not revealed how this regulation of expression is controlled. In this review, we propose that planarians represent a unique and effective system to study the epigenetic regulation of these processes in an in vivo context...
April 22, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29680681/hdac-inhibition-helps-post-mi-healing-by-modulating-macrophage-polarization
#14
Denise Kimbrough, Sabina H Wang, Lillianne H Wright, Santhosh K Mani, Harinath Kasiganesan, Amanda C LaRue, Qi Cheng, Satish N Nadig, Carl Atkinson, Donald R Menick
AIMS: Following an acute myocardial infarction (MI) the extracellular matrix (ECM) undergoes remodeling in order to prevent dilation of the infarct area and maintain cardiac output. Excessive and prolonged inflammation following an MI exacerbates adverse ventricular remodeling. Macrophages are an integral part of the inflammatory response that contribute to this remodeling. Treatment with histone deacetylase (HDAC) inhibitors preserves LV function and myocardial remodeling in the post-MI heart...
April 19, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29678683/long-term-affected-flat-oyster-ostrea-edulis-haemocytes-show-differential-gene-expression-profiles-from-na%C3%A3-ve-oysters-in-response-to-bonamia-ostreae
#15
P Ronza, A Cao, D Robledo, A Gómez-Tato, J A Álvarez-Dios, A F M Hasanuzzaman, M I Quiroga, A Villalba, B G Pardo, P Martínez
European flat oyster (Ostrea edulis) production has suffered a severe decline due to bonamiosis. The responsible parasite enters in oyster haemocytes, causing an acute inflammatory response frequently leading to death. We used an immune-enriched oligo-microarray to understand the haemocyte response to Bonamia ostreae by comparing expression profiles between naïve (NS) and long-term affected (AS) populations along a time series (1 d, 30 d, 90 d). AS showed a much higher response just after challenge, which might be indicative of selection for resistance...
April 17, 2018: Genomics
https://www.readbyqxmd.com/read/29674394/acetyl-coa-promotes-glioblastoma-cell-adhesion-and-migration-through-ca-2-nfat-signaling
#16
Joyce V Lee, Corbett T Berry, Karla Kim, Payel Sen, Taehyong Kim, Alessandro Carrer, Sophie Trefely, Steven Zhao, Sully Fernandez, Lauren E Barney, Alyssa D Schwartz, Shelly R Peyton, Nathaniel W Snyder, Shelley L Berger, Bruce D Freedman, Kathryn E Wellen
The metabolite acetyl-coenzyme A (acetyl-CoA) is the required acetyl donor for lysine acetylation and thereby links metabolism, signaling, and epigenetics. Nutrient availability alters acetyl-CoA levels in cancer cells, correlating with changes in global histone acetylation and gene expression. However, the specific molecular mechanisms through which acetyl-CoA production impacts gene expression and its functional roles in promoting malignant phenotypes are poorly understood. Here, using histone H3 Lys27 acetylation (H3K27ac) ChIP-seq (chromatin immunoprecipitation [ChIP] coupled with next-generation sequencing) with normalization to an exogenous reference genome (ChIP-Rx), we found that changes in acetyl-CoA abundance trigger site-specific regulation of H3K27ac, correlating with gene expression as opposed to uniformly modulating this mark at all genes...
April 19, 2018: Genes & Development
https://www.readbyqxmd.com/read/29673593/augmented-neutrophil-extracellular-traps-formation-promotes-atherosclerosis-development-in-socially-defeated-apoe-mice
#17
Keita Yamamoto, Hiroyuki Yamada, Noriyuki Wakana, Masakazu Kikai, Kensuke Terada, Naotoshi Wada, Shinichiro Motoyama, Makoto Saburi, Takeshi Sugimoto, Daisuke Kami, Takehiro Ogata, Masakazu Ibi, Chihiro Yabe-Nishimura, Satoaki Matoba
Depression is an independent risk factor of cardiovascular disease (CVD); however, the causal association remains undefined. We exposed mice to repeated social defeat (RSD) to precipitate depressive-like behaviors, and investigated the effects on atherosclerosis. Eight-week-old male apoE-/- mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days and fed a high-cholesterol diet (HCD) for 6 weeks. The social interaction ratio and immobility time showed dramatic social avoidance before and after HCD feeding...
June 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29672788/neutrophil-extracellular-traps-participate-in-all-different-types-of-thrombotic-and-haemorrhagic-complications-of-coronary-atherosclerosis
#18
Kartika R Pertiwi, Allard C van der Wal, Dara R Pabittei, Claire Mackaaij, Marinus B van Leeuwen, Xiaofei Li, Onno J de Boer
Acute coronary syndromes can be initiated by either atherosclerotic fibrous cap ruptures, superficial plaque erosions or intraplaque haemorrhages (IPHs). Since neutrophil extracellular traps (NETs) display pro-inflammatory and pro-thrombotic properties, we investigated the presence, extent and distribution of neutrophils and NETs in different types of plaque complications in relation to the age of overlying thrombus mass or haemorrhage. Sixty-four paraffin-embedded coronary plaque segments of 30 acute myocardial infarction patients were retrieved from the autopsy archives, which contained 44 complicated plaques (17 IPHs, 9 erosions and 18 ruptures) and 20 intact plaques...
April 19, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29670886/lncrnas-proverbial-genomic-junk-or-key-epigenetic-regulators-during-cardiac-fibrosis-in-diabetes
#19
Saumik Biswas, Anu Alice Thomas, Subrata Chakrabarti
Long non-coding RNAs (lncRNAs) are critical regulators in a multitude of biological processes. Recent evidences demonstrate potential pathogenetic implications of lncRNAs in diabetic cardiomyopathy (DCM); however, the majority of lncRNAs have not been comprehensively characterized. While the precise molecular mechanisms underlying the functions of lncRNAs remain to be deciphered in DCM, emerging data in other pathophysiological conditions suggests that lncRNAs can have versatile features such as genomic imprinting, acting as guides for certain histone-modifying complexes, serving as scaffolds for specific molecules, or acting as molecular sponges...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29669440/thrombin-generation-assay-detects-moderate-intensity-statin-induced-reduction-of-hypercoagulability-in-diabetes
#20
Hee Sue Park, Ja-Yoon Gu, Hyun Ju Yoo, Se Eun Han, Chan Ho Park, Young Il Kim, Il Sung Nam-Goong, Eun Sook Kim, Hyun Kyung Kim
Statins not only have a lipid-lowering effect but also reduce inflammation and have an antithrombotic effect. Since hypercoagulability assessed by thrombin generation assay (TGA) and increased formation of neutrophil extracellular traps (NET) were demonstrated in diabetes, we investigated whether statin therapy in diabetes modifies coagulation status and NET formation. Twenty-five consecutive patients with diabetes were recruited. Global coagulation assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], and TGA) and NET markers (DNA-histone complex, cell-free DNA, and neutrophil elastase) were measured before and after 3-month moderate-intensity statin therapy...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
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