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https://www.readbyqxmd.com/read/28212747/catalytic-independent-functions-of-parp-1-determine-sox2-pioneer-activity-at-intractable-genomic-loci
#1
Ziying Liu, W Lee Kraus
Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity...
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
#2
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/28208804/hazelnut-corylus-avellana-l-shells-extract-phenolic-composition-antioxidant-effect-and-cytotoxic-activity-on-human-cancer-cell-lines
#3
Tiziana Esposito, Francesca Sansone, Silvia Franceschelli, Pasquale Del Gaudio, Patrizia Picerno, Rita Patrizia Aquino, Teresa Mencherini
Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207569/poly-adp-ribose-polymerase-inhibition-suppresses-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#4
Ling-Yi Xiao, Wai-Ming Kan
Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib...
March 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28202539/parps-and-adp-ribosylation-recent-advances-linking-molecular-functions-to-biological-outcomes
#5
REVIEW
Rebecca Gupte, Ziying Liu, W Lee Kraus
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28190768/serine-adp-ribosylation-depends-on-hpf1
#6
Juan José Bonfiglio, Pietro Fontana, Qi Zhang, Thomas Colby, Ian Gibbs-Seymour, Ilian Atanassov, Edward Bartlett, Roko Zaja, Ivan Ahel, Ivan Matic
ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. However, the biochemical basis underlying this serine modification remained unknown. Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28181505/parp-1-parp-2-double-deficiency-in-mouse-t-cells-results-in-faulty-immune-responses-and-t-lymphomas
#7
Judith Navarro, Beatriz Gozalbo-López, Andrea C Méndez, Françoise Dantzer, Valérie Schreiber, Carlos Martínez, David M Arana, Jordi Farrés, Beatriz Revilla-Nuin, María F Bueno, Coral Ampurdanés, Miguel A Galindo-Campos, Philip A Knobel, Sandra Segura-Bayona, Juan Martin-Caballero, Travis H Stracker, Pedro Aparicio, Margarita Del Val, José Yélamos
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177666/poly-adp-ribose-polymerase-1-parp-1-in-chinese-patients-with-graves-disease-and-graves-ophthalmopathy
#8
Tong Wu, Dong-Run Tang, Liang Zhao, Feng-Yuan Sun
We aimed to evaluate the genetic variation of poly (ADP-ribose) polymerase-1 (PARP-1) as risk factor in development of Graves' disease (GD) and Graves Ophthalmopathy (GO) among Chinese individuals. Patients with confirmed diagnosis of GD or healthy individuals with no clinical symptoms of hyperthyroiditis were enrolled at department of Ophthalmology, Tianjin First Center Hospital, China. Genetic polymorphism was studied in plasma DNA samples of subjects by polymererase chain reaction of restriction fragment length polymorphism to confirm test our hypothesis...
January 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28177129/role-of-parp-activity-in-lung-cancer-induced-cachexia-effects-on-muscle-oxidative-stress-proteolysis-anabolic-markers-and-phenotype
#9
Alba Chacon-Cabrera, Mercè Mateu-Jimenez, Klaus Langohr, Clara Fermoselle, Elena García-Arumí, Antoni L Andreu, Jose Yelamos, Esther Barreiro
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1(-/-) ) and Parp-2(-/-) mice...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28159921/curcumin-blocks-autophagy-and-activates-apoptosis-of-malignant-mesothelioma-cell-lines-and-increases-the-survival-of-mice-intraperitoneally-transplanted-with-a-malignant-mesothelioma-cell-line
#10
Laura Masuelli, Monica Benvenuto, Enrica Di Stefano, Rosanna Mattera, Massimo Fantini, Giuseppina De Feudis, Enrico De Smaele, Ilaria Tresoldi, Maria Gabriella Giganti, Andrea Modesti, Roberto Bei
Malignant mesothelioma (MM) is a primary tumor arising from the serous membranes. The resistance of MM patients to conventional therapies, and the poor patients' survival, encouraged the identification of molecular targets for MM treatment. Curcumin (CUR) is a "multifunctional drug". We explored the in vitro effects of CUR on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, autophagy of human (MM-B1, H-Meso-1, MM-F1), and mouse (#40a) MM cells. In addition, we evaluated the in vivo anti-tumor activities of CUR in C57BL/6 mice intraperitoneally transplanted with #40a cells forming ascites...
30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28140659/protective-effect-of-mild-induced-hypothermia-against-moderate-traumatic-brain-injury-in-rats-involved-in-necroptotic-and-apoptotic-pathways
#11
Hai-Bo Zhang, Shi-Xiang Cheng, Yue Tu, Sai Zhang, Shi-Ke Hou, Zhen Yang
AIM: To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis. METHODS: Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypothermia (TBI+HT). The sham+HT and TBI+HT groups were submitted to 32°C for 6 hours...
January 31, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28131694/neer-award-2016-reduced-muscle-degeneration-and-decreased-fatty-infiltration-after-rotator-cuff-tear-in-a-poly-adp-ribose-polymerase-1-parp-1-knock-out-mouse-model
#12
Michael B Kuenzler, Katja Nuss, Agnieszka Karol, Michael O Schär, Michael Hottiger, Sumit Raniga, David Kenkel, Brigitte von Rechenberg, Matthias A Zumstein
BACKGROUND: Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model...
January 25, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28131528/expression-of-dna-damage-response-proteins-in-cervical-cancer-patients-treated-with-radical-chemoradiotherapy
#13
C K Ho, E N Kornaga, A C Klimowicz, E K Enwere, M Dean, G D Bebb, T Phan, P Ghatage, A M Magliocco, S P Lees-Miller, C M Doll
OBJECTIVE: The management of locally advanced cervical cancer has improved significantly with the advent of cisplatin-based chemoradiotherapy (CRT) as the primary treatment regimen. Nevertheless, a significant proportion of patients fail to respond or relapse on this treatment and have a very poor prognosis. Our goal was to determine the prognostic value of a panel of proteins involved in detection and repair of DNA damage. METHODS: We performed fluorescence immunohistochemistry, and used software analysis to assess expression of DNA damage response proteins ATM, DNA-PKcs, PARP-1, Ku70 and Ku86 in 117 pre-treatment specimens from patients with locally advanced cervical cancer...
January 25, 2017: Gynecologic Oncology
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
#14
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/28122037/novel-parp-1-inhibitor-scaffolds-disclosed-by-a-dynamic-structure-based-pharmacophore-approach
#15
Salete J Baptista, Maria M C Silva, Elisabetta Moroni, Massimiliano Meli, Giorgio Colombo, Teresa C P Dinis, Jorge A R Salvador
PARP-1 inhibition has been studied over the last decades for the treatment of various diseases. Despite the fact that several molecules act as PARP-1 inhibitors, a reduced number of compounds are used in clinical practice. To identify new compounds with a discriminatory PARP-1 inhibitory function, explicit-solvent molecular dynamics simulations using different inhibitors bound to the PARP-1 catalytic domain were performed. The representative structures obtained were used to generate structure-based pharmacophores, taking into account the dynamic features of receptor-ligand interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28120709/dna-damaging-anticancer-drugs-a-perspective-for-dna-repair-oriented-therapy
#16
Janusz Blasiak
DNA-damaging drugs in cancer present two main problems: therapeutic resistance and side effects and both can associate with DNA repair, which can be targeted in cancer therapy. Bleomycin (BLM) induces complex DNA damages, including strand breaks, base loss and 3'-phosphoglycolate (3'PG) residues repaired by several pathways, but 3'PGs must be processed to the 3'-OH ends, usually by tyrosyl-DNA phosphodiesterase 1 (Tdp1). Therefore, targeting Tdp1 can improve anticancer therapy with BLM. Mitomycin C (MMC) produces a variety of adducts with DNA, including inter-strand cross-links (ICLs) and Xeroderma pigmentosum (XP) proteins, including XPG, XPE and XPF can be crucial for the initial stage of ICL repair, so they can be targeted by inhibitors to increase toxicity of MMC in cancer cells...
January 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28118040/parp-1-expression-quantified-by-18-f-fluorthanatrace-a-biomarker-of-response-to-parp-inhibition-adjuvant-to-radiation-therapy
#17
Samuel Sander Effron, Mehran Makvandi, Lilie Lin, Kuiying Xu, Shihong Li, Hsiaoju Lee, Catherine Hou, Daniel A Pryma, Cameron Koch, Robert H Mach
INTRODUCTION: Poly (ADP-ribose) polymerase 1 (PARP-1) is the major target of clinical PARP inhibitors and is a potential predictive biomarker for response to therapy. Due to the limited success of PARP inhibitors as monotherapy, investigators have shifted the clinical role of PARP inhibitors to the adjuvant setting. In this study, we evaluate the radiotracer [(18)F]FluorThanatrace ([(18)F]FTT) as a marker of PARP expression in vitro and the associated biological implications of PARP-1 expression in PARP inhibitor treatment adjuvant to radiation therapy...
February 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28108258/downregulation-of-iduna-is-associated-with-aif-nuclear-translocation-in-neonatal-brain-after-hypoxia-ischemia
#18
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/28107648/parp-1-controls-the-adipogenic-transcriptional-program-by-parylating-c-ebp%C3%AE-and-modulating-its-transcriptional-activity
#19
Xin Luo, Keun Woo Ryu, Dae-Seok Kim, Tulip Nandu, Carlos J Medina, Rebecca Gupte, Bryan A Gibson, Raymond E Soccio, Yonghao Yu, Rana K Gupta, W Lee Kraus
Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPβ's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107013/quaternary-n-2-pyridyl-dabco-salts-one-pot-in-situ-formation-from-pyridine-n-oxides-and-reactions-with-nucleophiles-a-mild-and-selective-route-to-substituted-n-2-pyridyl-n-ethylpiperazines
#20
Dmitry I Bugaenko, Marina A Yurovskaya, Alexander V Karchava
The N-(2-pyridyl)-N'-ethylpiperazines are important structural motifs in several medicinally relevant compounds. Known synthetic methods toward these structures are multistep and generally based on the SNAr-chemistry; their applicability is significantly limited to substrates containing electron-withdrawing groups. Here, we describe a new methodology for a rapid and modular access to this privileged scaffold. Importantly, the developed protocol proved to be very general and efficient for the substrates containing substituents of different electronic nature...
January 30, 2017: Journal of Organic Chemistry
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