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https://www.readbyqxmd.com/read/28228717/mild-hypothermia-attenuates-the-anesthetic-isoflurane-induced-cytotoxicity
#1
Cheng Li, Yuanlin Dong, Dan Chen, Zhongcong Xie, Yiying Zhang
The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#2
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28176872/genotoxic-effects-of-culture-media-on-human-pluripotent-stem-cells
#3
Megha Prakash Bangalore, Syama Adhikarla, Odity Mukherjee, Mitradas M Panicker
Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#4
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28127258/tnf-%C3%AE-sensitizes-chemotherapy-and-radiotherapy-against-breast-cancer-cells
#5
Xiao Wu, Meng-Yao Wu, Min Jiang, Qiaoming Zhi, Xiaojie Bian, Meng-Dan Xu, Fei-Ran Gong, Juan Hou, Min Tao, Liu-Mei Shou, Weiming Duan, Kai Chen, Meng Shen, Wei Li
PURPOSE: Despite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28098861/triptolide-inhibits-viability-and-induces-apoptosis-in-liver-cancer-cells-through-activation-of-the-tumor-suppressor-gene-p53
#6
Yan-Yan Sun, Lei Xiao, Dong Wang, Yan-Chao Ji, Yu-Peng Yang, Rong Ma, Xi-Hai Chen
The present study investigated the effect of triptolide on viability and apoptosis along with underlying mechanism in liver cancer cells. CCK-8 assay showed that triptolide treatment for 48 h significantly reduced the viability of HepG2 and QSG7701 cells at 50 µM concentration. Annexin V-FITC and propidium iodide staining showed that triptolide treatment of HepG2 cells at 50 µM concentrations induced apoptosis in 56.45% cells compared to only 2.36% cells in the control cultures. Western blot assay showed that treatment of HepG2 cells with 50 µM concentration of triptolide significantly induced phosphorylation of p53 in a 2 h-treatment...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098859/dna-damage-response-defect-in-williams-beuren-syndrome
#7
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28038734/partially-assembled-nucleosome-structures-at%C3%A2-atomic-detail
#8
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28028239/asymmetric-unwrapping-of-nucleosomal-dna-propagates-asymmetric-opening-and-dissociation-of-the-histone-core
#9
Yujie Chen, Joshua M Tokuda, Traci Topping, Steve P Meisburger, Suzette A Pabit, Lisa M Gloss, Lois Pollack
The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27994550/anti-proliferative-and-apoptosis-inducing-effect-of-theabrownin-against-non-small-cell-lung-adenocarcinoma-a549-cells
#10
Feifei Wu, Li Zhou, Wangdong Jin, Weiji Yang, Ying Wang, Bo Yan, Wenlin Du, Qiang Zhang, Lei Zhang, Yonghua Guo, Jin Zhang, Letian Shan, Thomas Efferth
With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27959435/oridonin-promotes-g2-m-arrest-in-a549-cells-by-facilitating-atm-activation
#11
Mingxing Zheng, Zhibing Zhu, Yongzhao Zhao, Da Yao, Maoqing Wu, Gengyun Sun
Previous studies have demonstrated that oridonin, a tetracyclic diterpenoid compound extracted from Rabdosia rubescens, inhibits proliferation and induces apoptosis in several tumor cell lines. However, the mechanism by which oridonin inhibits the cell cycle remains poorly understood. In the present study, possible mechanisms by which oridonin affects cell cycle progression were explored in A549 lung cancer cells. Flow cytometry analysis indicated that oridonin inhibited the proliferation of A549 cells by inducing G2/M cell cycle arrest in a dose‑dependent manner...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27941214/calcium-alterations-signal-either-to-senescence-or-to-autophagy-induction-in-stem-cells-upon-oxidative-stress
#12
Aleksandra V Borodkina, Alla N Shatrova, Pavel I Deryabin, Anastasiia A Griukova, Polina A Abushik, Sergei M Antonov, Nikolay N Nikolsky, Elena B Burova
Intracellular calcium ([Ca(2+)]i) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca(2+)]i contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H2O2-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway. Notably, further senescence development was accompanied by persistently elevated [Ca(2+)]i levels...
December 8, 2016: Aging
https://www.readbyqxmd.com/read/27939754/increasing-no-level-regulates-apoptosis-and-inflammation-in-macrophages-after-2-chloroethyl-ethyl-sulphide-challenge
#13
Satish Sagar, Soumya Ranjan Parida, Silpa Sabnam, Huma Rizwan, Sweta Pal, Mitali Madhusmita Swain, Arttatrana Pal
Generation of nitric oxide (NO) in cellular compartments acts in a redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging superoxide anions (O2(-)), to form peroxynitrite (ONOO-) or acting as a signaling molecule, altering gene expression that triggers various physiological processes. However, the molecular mechanisms of macrophage activation and NO production leads to apoptosis and inflammation after 2-chloroethyl ethyl sulphide (CEES) exposure remains unclear...
December 9, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27827373/bmi1-regulates-prc1-architecture-and-activity-through-homo-and-hetero-oligomerization
#14
Felicia Gray, Hyo Je Cho, Shirish Shukla, Shihan He, Ashley Harris, Bohdan Boytsov, Łukasz Jaremko, Mariusz Jaremko, Borries Demeler, Elizabeth R Lawlor, Jolanta Grembecka, Tomasz Cierpicki
BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein-protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a β-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27813335/phosphorylation-of-h2a-x-t-yr39-positively-regulates-dna-damage-response-and-is-linked-to-cancer-progression
#15
EDITORIAL
Yan Liu, Yue-Hong Long, Shu-Qing Wang, Yu-Feng Li, Jing-Hua Zhang
Double-stranded DNA breaks induce serine phosphorylation of histone H2A.X, producing γ-H2A.X foci that are then recognized by DNA damage response pathway proteins. Formation of γ-H2A.X is therefore critical for the repair of DNA double-stranded breaks and maintenance of genomic stability, and defects in the recognition or repair of double-stranded breaks can result in tumorigenesis. However, key details regarding the formation of γ-H2A.X and its possible role in tumorigenesis remain elusive. Here, we report a previously unknown phosphorylation site on H2A...
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27798884/high-expression-of-mre11-rad50-nbs1-is-associated-with-poor-prognosis-and-chemoresistance-in-gastric-cancer
#16
Bolag Altan, Takehiko Yokobori, Munenori Ide, Tuya Bai, Toru Yanoma, Akiharu Kimura, Norimichi Kogure, Masaki Suzuki, Pinjie Bao, Erito Mochiki, Kyoichi Ogata, Tadashi Handa, Kyoichi Kaira, Masahiko Nishiyama, Takayuki Asao, Tetsunari Oyama, Hiroyuki Kuwano
BACKGROUND: The MRN complex of meiotic recombination 11 (MRE11), DNA repair protein Rad50 (RAD50) and Nijmegen breakage syndrome 1 (NBS1) proteins coordinate the detection and repair of DNA double-strand breaks (DSBs). DNA DSB repair-dependent chemoresistance likely has an effect on the treatment of human cancer. MATERIALS AND METHODS: We investigated the expression of MRN complex in human gastric cancer (GC) tissues using immunohistochemistry and analyzed its clinical significance and prognostic relevance...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27773672/cyclin-f-mediated-degradation-of-slbp-limits-h2a-x-accumulation-and-apoptosis-upon-genotoxic-stress-in-g2
#17
John F Dankert, Gergely Rona, Linda Clijsters, Phillip Geter, Jeffrey R Skaar, Keria Bermudez-Hernandez, Elizabeth Sassani, David Fenyö, Beatrix Ueberheide, Robert Schneider, Michele Pagano
SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27720638/genetic-modification-of-h2ax-renders-mesenchymal-stromal-cell-derived-dopamine-neurons-more-resistant-to-dna-damage-and-subsequent-apoptosis
#18
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
https://www.readbyqxmd.com/read/27672100/dna-damage-response-induces-structural-alterations-in-histone-h3-h4
#19
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
https://www.readbyqxmd.com/read/27661115/ibrutinib-synergizes-with-mdm-2-inhibitors-in-promoting-cytotoxicity-in-b-chronic-lymphocytic-leukemia
#20
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
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