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https://www.readbyqxmd.com/read/28216620/aspirin-alleviates-cardiac-fibrosis-in-mice-by-inhibiting-autophagy
#1
Ping-Ping Liu, Hong-Hong Liu, Shu-Hong Sun, Xing-Xing Shi, Wan-Cheng Yang, Guo-Hai Su, Jing Zhao
Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg(-1)·d(-1), ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28212744/parp1-and-sox2-an-unlikely-team-of-pioneers-to-conquer-the-nucleosome
#2
Guillaume Gaullier, Karolin Luger
In this issue of Molecular Cell, Liu and Kraus (2017) demonstrate that the pioneer transcription factor Sox2 requires PARP1 to bind to a subset of its recognition motifs, which are located within nucleosomes across the genome.
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28212373/poly-adp-ribose-polymerase-1-mrna-levels-strongly-correlate-with-the-prognosis-of-myelodysplastic-syndromes
#3
P Diamantopoulos, K Zervakis, P Zervakis, M Sofotasiou, T Vassilakopoulos, I Kotsianidis, A Symeonidis, V Pappa, A Galanopoulos, E Solomou, E Kodandreopoulou, V Papadopoulou, P Korkolopoulou, M Mantzourani, G Kyriakakis, N-A Viniou
Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28202508/chemosensitivity-of-idh1-mutant-gliomas-due-to-an-impairment-in-parp1-mediated-dna-repair
#4
Yanxin Lu, Jakub Kwintkiewicz, Yang Liu, Katherine Tech, Lauren N Frady, Yu-Ting Su, Wendy Bautista, Seog In Moon, Jeffrey MacDonald, Matthew G Edwend, Mark R Gilbert, Chunzhang Yang, Jing Wu
Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD+ availability...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#5
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28182794/identification-of-several-high-risk-hpv-inhibitors-and-drug-targets-with-a-novel-high-throughput-screening-assay
#6
Mart Toots, Mart Ustav, Andres Männik, Karl Mumm, Kaido Tämm, Tarmo Tamm, Ene Ustav, Mart Ustav
Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28159922/base-excision-repair-imbalance-in-colorectal-cancer-has-prognostic-value-and-modulates-response-to-chemotherapy
#7
Natalia M Leguisamo, Helena C Gloria, Antonio N Kalil, Talita V Martins, Daniel B Azambuja, Lisiane B Meira, Jenifer Saffi
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients' clinical and pathological features...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28150715/epigenetic-regulation-of-nitric-oxide-synthase-2-inducible-nos2-by-nlrc4-inflammasomes-involves-parp1-cleavage
#8
Carina de Lima Buzzo, Tiago Medina, Laura M Branco, Silvia L Lage, Luís Carlos de Souza Ferreira, Gustavo P Amarante-Mendes, Michael O Hottiger, Daniel D De Carvalho, Karina R Bortoluci
Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role for NLRC4/caspase-1 axis in regulating chromatin accessibility of the Nos2 promoter. We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and NF-κB activation...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150709/the-conserved-macrodomains-of-the-non-structural-proteins-of-chikungunya-virus-and-other-pathogenic-positive-strand-rna-viruses-function-as-mono-adp-ribosylhydrolases
#9
Laura Eckei, Sarah Krieg, Mareike Bütepage, Anne Lehmann, Annika Gross, Barbara Lippok, Alexander R Grimm, Beate M Kümmerer, Giulia Rossetti, Bernhard Lüscher, Patricia Verheugd
Human pathogenic positive single strand RNA ((+)ssRNA) viruses, including Chikungunya virus, pose severe health problems as for many neither efficient vaccines nor therapeutic strategies exist. To interfere with propagation, viral enzymatic activities are considered potential targets. Here we addressed the function of the viral macrodomains, conserved folds of non-structural proteins of many (+)ssRNA viruses. Macrodomains are closely associated with ADP-ribose function and metabolism. ADP-ribosylation is a post-translational modification controlling various cellular processes, including DNA repair, transcription and stress response...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28130107/extracellular-poly-adp-ribose-is-a-neurotrophic-signal-that-upregulates-glial-cell-line-derived-neurotrophic-factor-gdnf-levels-in%C3%A2-vitro-and-in%C3%A2-vivo
#10
Hidemitsu Nakajima, Masanori Itakura, Keishi Sato, Sunao Nakamura, Yasu-Taka Azuma, Tadayoshi Takeuchi
Synthesis of poly(ADP-ribose) (PAR) is catalyzed by PAR polymerase-1 (PARP-1) in neurons. PARP1 plays a role in various types of brain damage in neurodegenerative disorders. In neurons, overactivation of PARP-1 during oxidative stress induces robust PAR formation, which depletes nicotinamide adenine dinucleotide levels and leads to cell death. However, the role of the newly-formed PAR in neurodegenerative disorders remains elusive. We hypothesized that the effects of PAR could occur in the extracellular space after it is leaked from damaged neurons...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129013/oxidative-dna-damage-and-reduced-expression-of-dna-repair-genes-role-in-primary-open-angle-glaucoma-poag
#11
Kuldeep Mohanty, Rima Dada, Tanuj Dada
BACKGROUND: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis. MATERIALS AND METHODS: The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA...
January 27, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28128733/actein-inhibits-glioma-growth-via-a-mitochondria-mediated-pathway
#12
Li-Qun Yuan, Yan-Ming Chen, Chao Sun, Zhong-Yong Wang, De-Lin Wang, Qing Lan
Previous studies indicate that the triterpene glycoside Actein from the herb black cohosh inhibits growth of human breast cancer cells. This study sought to investigate the effects of Actein on glioma cell growth and explore the potential mechanisms. Our results showed that administration of Actein significantly inhibited glioma cell viability in a dose- and time-dependent manner. Actein also increasingly inhibited the colony formation processes in glioma U87 cells and U251 cells. Administration of Actein also induced mitochondria-related apoptosis by increasing expression of pro-apoptotic factors Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) as well as decreasing anti-apoptotic Bcl-2 expression in U87 cells and U251 cells...
January 20, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28108511/biomarker-based-pet-imaging-of-diffuse-intrinsic-pontine-glioma-in-mouse-models
#13
Susanne Kossatz, Brandon Carney, Melanie E Schweitzer, Giuseppe Carlucci, Vesselin Miloushev, Uday B Maachani, Prajwal Rajappa, Kayvan Keshari, David J Pisapia, Wolfgang A Weber, Mark M Souweidane, Thomas Reiner
Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize on a positron emission tomography (PET) probe for imaging DIPG in vivo. In human histological tissues, the probes target, poly(ADP)ribose polymerase 1 (PARP1), was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model (GEMM), and probe uptake correlated to histologically determined tumor infiltration...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108258/downregulation-of-iduna-is-associated-with-aif-nuclear-translocation-in-neonatal-brain-after-hypoxia-ischemia
#14
Xiaoxia Yang, Jianhua Cheng, Yubo Gao, Juan Ding, Xinli Ni
In adult stroke models, the neuroprotective protein, Iduna, inhibits poly (ADP-ribose) polymerase-1 (PARP-1)-dependent cell death by decreasing apoptosis-inducing factor (AIF) nuclear translocation. Because the PARP1-dependent pathway and Iduna, which promotes AIF degradation, contribute to hypoxic-ischemic (HI) brain damage in the immature brain, we examined the relationship between Iduna expression and AIF nuclear translocation in the cerebral cortex of postnatal day 7 rats after HI. Ninety rats were divided into three groups: sham, 1-h hypoxia and 2-h hypoxia...
January 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28105679/robust-immunoglobulin-class-switch-recombination-and-end-joining-in-parp9-deficient-mice
#15
Isabelle Robert, Léa Gaudot, Jose Yelamos, Aurélia Noll, Heng-Kuan Wong, Françoise Dantzer, Valérie Schreiber, Bernardo Reina-San-Martin
To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving Poly(ADP-ribose) polymerases Parp1, Parp2 and Parp3 to promote appropriate DNA repair and efficient long-range recombination...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28100769/the-ubiquitin-like-with-phd-and-ring-finger-domains-1-uhrf1-dna-methyltransferase-1-dnmt1-axis-is-a-primary-regulator-of-cell-senescence
#16
Hyun-Jung Jung, Hae-Ok Byun, Byul A Jee, Seongki Min, Un-Woo Jeoun, Young-Kyoung Lee, Yonghak Seo, Hyun Goo Woo, Gyesoon Yoon
As senescence develops, cells sequentially acquire diverse senescent phenotypes, along with simultaneous multi-stage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analysed time-series gene expression profiles obtained in two different senescence models in human diploid fibroblasts (HDF): replicative senescence and H2O2-induced senescence. Our results demonstrated that suppression of DNA methyltransferase 1 (DNMT1)-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#17
Erin George, Hyoung Kim, Clemens Krepler, Brandon Wenz, Mehran Makvandi, Janos L Tanyi, Eric Brown, Rugang Zhang, Patricia Brafford, Stephanie Jean, Robert H Mach, Yiling Lu, Gordon B Mills, Meenhard Herlyn, Mark Morgan, Xiaochen Zhang, Robert Soslow, Ronny Drapkin, Neil Johnson, Ying Zheng, George Cotsarelis, Katherine L Nathanson, Fiona Simpkins
Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#18
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28087741/14-3-3sigma-contributes-to-radioresistance-by-regulating-dna-repair-and-cell-cycle-via-parp1-and-chk2
#19
Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian-Ting Zhang
: 14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28069995/atm-induces-macrod2-nuclear-export-upon-dna-damage
#20
Barbara Golia, Giuliana Katharina Moeller, Gytis Jankevicius, Andreas Schmidt, Anna Hegele, Julia Preißer, Mai Ly Tran, Axel Imhof, Gyula Timinszky
ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity...
January 9, 2017: Nucleic Acids Research
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