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Peizhou Jiang, Peng Huang, Shu-Hui Yen, Abba C Zubair, Dennis W Dickson
BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients...
October 6, 2016: Cytotherapy
Yudai Izumi, Kentaro Fujii, Satoshi Yamamoto, Koichi Matsuo, Hirofumi Namatame, Masaki Taniguchi, Akinari Yokoya
Synchrotron-radiation circular-dichroism spectroscopy was used to reveal that the DNA damage response induces a decrement of α-helix and an increment of β-strand contents of histone H3-H4 extracted from X-ray-irradiated human HeLa cells. The trend of the structural alteration was qualitatively opposite to that of our previously reported results for histone H2A-H2B. These results strongly suggest that histones share roles in DNA damage responses, particularly in DNA repair processes and chromatin remodeling, via a specific structural alteration of each histone...
September 26, 2016: Journal of Radiation Research
Rebecca Voltan, Erika Rimondi, Elisabetta Melloni, Gian Matteo Rigolin, Fabio Casciano, Maria Vittoria Arcidiacono, Claudio Celeghini, Antonio Cuneo, Giorgio Zauli, Paola Secchiero
OBJECTIVE: The aim of this study was to investigate the anti-leukemic activity of the Bruton tyrosine kinase inhibitor Ibrutinib in combination with the small molecule MDM-2 inhibitor Nutlin-3 in preclinical models. METHODS: The potential efficacy of the Ibrutinib/Nutlin-3 combination was evaluated in vitro in a panel of B leukemic cell lines (EHEB, JVM-2, JVM-3, MEC-1, MEC-2) and in primary B-chronic lymphocytic leukemia (B-CLL) patient samples, by assessing cell viability, cell cycle profile, apoptosis and intracellular pathway modulations...
September 20, 2016: Oncotarget
G Ronald Jenkins, Taewon Lee, Carrie L Moland, Vikrant Vijay, Eugene H Herman, Sherry M Lewis, Kelly J Davis, Levan Muskhelishvili, Susan Kerr, James C Fuscoe, Varsha G Desai
Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F1 mice were dosed with 3mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24mg/kg cumulative doses...
November 1, 2016: Toxicology and Applied Pharmacology
Jingshuai Wang, Jiyang Li, Jie Liu, Mengjiao Xu, Xiaowen Tong, Jianjun Wang
Numerous clinical therapeutic agents have been identified as DNA damaging. The present study revealed that isoproterenol (Iso) resulted in DNA damage in vascular smooth muscle cells (VSMCs) and increased the levels of intracellular oxygen free radicals. Administration of chlorogenic acid (CGA) inhibited this effect. Pretreatment with CGA abrogated the increase in protein expression levels of γ‑H2A histone family member X, phosphorylated ataxia telangiectasia mutated, phosphorylated Rad3‑related protein, breast cancer 1 and C‑terminal Src homologous kinase induced by Iso...
September 15, 2016: Molecular Medicine Reports
Kensuke Kojima, Aya Maeda, Mariko Yoshimura, Yuki Nishida, Shinya Kimura
PPM1D is a serine/threonine phosphatase that negatively regulates key DNA damage response proteins, such as p53, p38 MAPK, histone H2A.X, and ATM. We investigated the pathophysiological significance of PPM1D and its therapeutic targeting by the novel PPM1D inhibitor GSK2830371 in mantle cell lymphoma (MCL). Oncomine-based analyses indicated increased PPM1D mRNA levels in MCL cells compared with their normal counterpart cells. Higher PPM1D expression was associated with higher expression of the proliferation gene signature and poorer prognosis in patients...
September 8, 2016: Oncotarget
Ciro Rivera-Casas, Rodrigo González-Romero, Ángel Vizoso-Vazquez, Manjinder S Cheema, M Esperanza Cerdán, Josefina Méndez, Juan Ausió, Jose M Eirin-Lopez
Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin...
October 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Anna Török, Philipp H Schiffer, Christine E Schnitzler, Kris Ford, James C Mullikin, Andreas D Baxevanis, Antony Bacic, Uri Frank, Sebastian G Gornik
BACKGROUND: Cnidarians are a group of early branching animals including corals, jellyfish and hydroids that are renowned for their high regenerative ability, growth plasticity and longevity. Because cnidarian genomes are conventional in terms of protein-coding genes, their remarkable features are likely a consequence of epigenetic regulation. To facilitate epigenetics research in cnidarians, we analysed the histone complement of the cnidarian model organism Hydractinia echinata using phylogenomics, proteomics, transcriptomics and mRNA in situ hybridisations...
2016: Epigenetics & Chromatin
Kenneth Börner, Peter B Becker
SWR1-type nucleosome remodeling factors replace histone H2A by variants to endow chromatin locally with specialized functionality. In Drosophila melanogaster a single H2A variant, H2A.V, combines functions of mammalian H2A.Z and H2A.X in transcription regulation and the DNA damage response. A major role in H2A.V incorporation for the only SWR1-like enzyme in flies, Domino, is assumed but not well documented in vivo. It is also unclear whether the two alternatively spliced isoforms, DOM-A and DOM-B, have redundant or specialized functions...
September 1, 2016: Development
Yung-Luen Shih, Jason Chou, Ming-Yang Yeh, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Hung-Sheng Shang, Fu-Shin Chueh, Yung-Lin Chu, Shu-Ching Hsueh, Jing-Gung Chung
Casticin, a polymethoxyflavone, has been demonstrated to possess anticancer activities, yet no study has shown in detail that casticin induces DNA damage in lung cancer cells. The purpose of this study was to investigate the possible molecular mechanisms of casticin which induce DNA damage and nuclear condensation in murine melanoma cancer B16F10 cells. In this study, by examining and capturing images using phase contrast microscopy, we found that casticin induced cell morphological changes. Moreover, it decreased the total number of viable cells which was measured by flow cytometry...
October 2016: Oncology Reports
Danielle Major, Rebecca S Derbes, He Wang, Astrid M Roy-Engel
Large quantities of dispersants were used as a method to disperse the roughly 210 million gallons of spilled crude oil that consumed the Gulf of Mexico. Little is known if the oil-dispersant and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to Corexit dispersants EC9500 and EC9527, Water Accommodated Fraction (WAF) -crude, WAF-9500 + Oil, and WAF-9527 + Oil...
June 2016: Gene Reports
Chabita Saha, Rahul Kumar, Asmita Das
Histones are associated with DNA to form nucleosome essential for chromatin structure and major nuclear processes like gene regulation and expression. Histones consist of H1, H2A, H2B and H3, H4 type proteins. In the present study combined histones from calf thymus were complexed with ct DNA and their binding affinities were measured fluorimetrically. All the five histones were resolved on SDS page and their binding with DNA was visualised. The values of biding affinities varied with pH and salt concentration...
August 17, 2016: Journal of Biomolecular Structure & Dynamics
Musaddiq J Awan, Jennifer Dorth, Arvind Mani, Haksoo Kim, Yiran Zheng, Mazen Mislmani, Scott Welford, Jiankui Yuan, Barry W Wessels, Simon S Lo, John Letterio, Mitchell Machtay, Andrew Sloan, Jason W Sohn
The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice...
July 21, 2016: Technology in Cancer Research & Treatment
Rafael Duran, Sahar Mirpour, Vasily Pekurovsky, Shanmugasundaram Ganapathy-Kanniappan, Cory F Brayton, Toby C Cornish, Boris Gorodetski, Juvenal Reyes, Julius Chapiro, Rüdiger E Schernthaner, Constantine Frangakis, MingDe Lin, Jessica D Sun, Charles P Hart, Jean-Francois Geschwind
PURPOSE: To evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intraarterial therapy (HAIAT) with evofosfamide in a rabbit model. EXPERIMENTAL DESIGN: VX2-tumor-bearing rabbits were assigned to 4 intraarterial therapy (IAT) groups (n=7/group): 1) saline (control); 2) evofosfamide (Evo); 3) doxorubicin-Lipiodol emulsion followed by embolization with 100-300μm beads (conventional, cTACE); or 4) cTACE and evofosfamide (cTACE+Evo). Blood samples were collected pre-IAT and 1/2/7/14 days post-IAT...
July 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yudai Izumi, Kentaro Fujii, Frank Wien, Chantal Houée-Lévin, Sandrine Lacombe, Daniela Salado-Leza, Erika Porcel, Rawand Masoud, Satoshi Yamamoto, Matthieu Réfrégiers, Marie-Anne Hervé du Penhoat, Akinari Yokoya
Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of α-helix structure and a decrease of β-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new α-helix structures at 310 K. We propose the structural transition from β-strand and turn structures to an α-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response...
July 12, 2016: Biophysical Journal
Xingzhu Ju, Shanhui Liang, Jun Zhu, Guihao Ke, Hao Wen, Xiaohua Wu
Our preliminary study found that CD147 is related to radioresistance and maybe an adverse prognostic factor in cervical cancer. To date, the mechanisms underlying CD147-induced radioresistance in cervical cancer remain unclear. In the present study, we investigated the mechanisms by which CD147 affects radiosensitivity in cervical cancer both in vitro and in vivo. In this study, the clonogenic assay showed that radiosensitivity was significantly higher in the experimental group (the CD147-negative cell lines) than in the control group (the CD147-positive cell lines)...
2016: American Journal of Translational Research
Wangbin Zhou, Juan Gao, Jing Ma, Lin Cao, Chi Zhang, Yan Zhu, Aiwu Dong, Wen-Hui Shen
Nuclear DNA homologous recombination (HR) occurs within the context of a highly complex chromatin structure. In spite of extensive studies of HR in diverse organisms, mechanisms regulating HR within chromatin context remain poorly elucidated. Here we investigate the role and interplay of the histone chaperones NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) and NAP1-RELATED PROTEIN (NRP) and the ATP-dependent chromatin-remodeling factor INOSITOL AUXOTROPHY80 (INO80) in regulating somatic HR in Arabidopsis thaliana. We show that simultaneous knockout of the four AtNAP1 genes and the two NRP genes in the sextuple mutant m123456-1 barely affects normal plant growth and development...
June 29, 2016: Plant Journal: for Cell and Molecular Biology
Clara Aceves-Luquero, Cristina Galiana-Roselló, Guillem Ramis, Ruth Villalonga-Planells, Enrique García-España, Silvia Fernández de Mattos, Rafael Peláez, José M Llinares, M Eugenia González-Rosende, Priam Villalonga
A series of compounds containing the sulfonamide scaffold were synthesized and screened for their in vitro anticancer activity against a representative panel of human cancer cell lines, leading to the identification of N-(2-methyl-1H-indol-5-yl)-1-naphthalenesulfonamide (8e) as a compound showing a remarkable activity across the panel, with IC50 values in the nanomolar-to-low micromolar range. Cell cycle distribution analysis revealed that 8e promoted a severe G2/M arrest, which was followed by cellular senescence as indicated by the detection of senescence-associated β-galactosidase (SA-β-gal) in 8e-treated cells...
September 1, 2016: Biochemical Pharmacology
Dong-Jie Li, Fang Huang, Min Ni, Hui Fu, Liang-Sheng Zhang, Fu-Ming Shen
OBJECTIVE: α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end-organ damage. In this study, we tested the role of α7nAChR in angiotensin II (Ang II)-induced senescence of vascular smooth muscle cells (VSMCs). APPROACH AND RESULTS: Expression of α7nAChR was not influenced by Ang II. Ang II induced remarkable senescent phenotypes in rodent and human VSMCs, including increased senescence-associated β-galactosidase activity, phosphorylation of H2A...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Urbain Weyemi, Christophe E Redon, Taresh K Sethi, Allison S Burrell, Parthav Jailwala, Manjula Kasoji, Natalie Abrams, Anand Merchant, William M Bonner
The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, which processes contribute to this remodeling remain poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and Zeb1 in human colon cancer cells. Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis...
September 16, 2016: Cell Cycle
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