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https://www.readbyqxmd.com/read/29667179/characteristics-of-genomic-alterations-of-lung-adenocarcinoma-in-young-never-smokers
#1
Wenxin Luo, Panwen Tian, Yue Wang, Heng Xu, Lu Chen, Chao Tang, Yang Shu, Shouyue Zhang, Zhoufeng Wang, Jun Zhang, Li Zhang, Lili Jiang, Lunxu Liu, Guowei Che, Chenglin Guo, Hong Zhang, Jiali Wang, Weimin Li
Non-small cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never-smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never-smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29661921/parp1-promotes-the-human-heat-shock-response-by-facilitating-hsf1-binding-to-dna
#2
Mitsuaki Fujimoto, Ryosuke Takii, Arpit Katiyar, Pratibha Srivastava, Akira Nakai
The heat shock response (HSR) is characterized by the rapid and robust induction of heat shock proteins (HSPs), including HSP70, in response to heat shock, and is regulated by heat shock transcription factor 1 (HSF1) in mammalian cells. Poly(ADP-ribose) polymerase 1 (PARP1), which can form a complex with HSF1 through the scaffold protein PARP13, has been suggested to be involved in the HSR. However, its effects on and regulatory mechanisms of the HSR are not well understood. Here, we show that prior to heat shock the HSF1-PARP13-PARP1 complex binds to HSP70 promoter...
April 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#3
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
April 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29627626/the-establishment-of-the-methods-for-free-par-generation-and-par-reader-detection
#4
Yueshuang Ke, Ke Wang, Hui Xu, Chenxin Wang, Jing Zhang, Xianlu Zeng, Ruoxi Wang, Istvan Boldogh, Xueqing Ba
Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor that catalyzes the poly (ADP-ribose) (PAR) onto a variety of target proteins, such as histones, DSB repair factors and PARP1 itself under consumption of NAD+ . Besides, PARP1 can affect a variety of proteins in noncovalent modification manner to carry out specific cellular functions. Here, we establishment a method to generate non-radiolabeled free PAR by PARG moderately cleaving PAR from autoPARylated PARP1, and utilize dot-blot assay to determine the interaction between free PAR and interested proteins...
April 5, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29626196/mutation-methylation-and-gene-expression-profiles-in-dup-1q-positive-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#5
Rebeqa Gunnarsson, Sebastian Dilorenzo, Kristina B Lundin-Ström, Linda Olsson, Andrea Biloglav, Henrik Lilljebjörn, Marianne Rissler, Per Wahlberg, Anders Lundmark, Anders Castor, Mikael Behrendtz, Thoas Fioretos, Kajsa Paulsson, Anders Isaksson, Bertil Johansson
High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs...
March 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29622868/bufalin-enhances-the-cytotoxity-of-human-multiple-myeloma-cells-h929-to-akt-inhibitor-mk2206-the-role-of-protein-akt-phosphorylation
#6
He Huang, Xiao-Ji Lin, Ying Lin, Ron-Xin Yao, Mu-Qing He
This study was purposed to investigate bufalin combined with AKT inhibitor MK2206 on growth inhibition and apoptosis of multiple myeloma cell line H929. CCK-8 assay and Annexin/PI staining were used to access the effects of bufalin and MK2206 in single or in combination, on inhibition of proliferation and induction of apoptosis in H929 cells. The apoptotic cells markedly increased after treated with nM bufalin and μM MK2206, including caspase3 and PARP1 proteins activated. The difference was statistically significant ( P  < 0...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29622785/author-correction-downregulation-of-parp1-transcription-by-promoter-associated-e2f4-rbl2-hdac1-brm-complex-contributes-to-repression-of-pluripotency-stem-cell-factors-in-human-monocytes
#7
Ewelina Wiśnik, Tomasz Płoszaj, Agnieszka Robaszkiewicz
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29617666/systematic-analysis-of-splice-site-creating-mutations-in-cancer
#8
Reyka G Jayasinghe, Song Cao, Qingsong Gao, Michael C Wendl, Nam Sy Vo, Sheila M Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H Payne, David Fenyö, Jeffrey H Miner, Matthew J Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29615218/placental-promoter-methylation-of-dna-repair-genes-and-prenatal-exposure-to-particulate-air-pollution-an-environage-cohort-study
#9
Kristof Y Neven, Nelly D Saenen, Letitzia Tarantini, Bram G Janssen, Wouter Lefebvre, Charlotte Vanpoucke, Valentina Bollati, Tim S Nawrot
BACKGROUND: Exposure to particulate air pollution has been linked with risk of carcinogenesis. Damage to repair pathways might have long-term adverse health effects. We aimed to investigate the association of prenatal exposure to air pollution with placental mutation rate and the DNA methylation of key placental DNA repair genes. METHODS: This cohort study used data from the ongoing ENVironmental Influence ON early AGEing (ENVIRONAGE) birth cohort, which enrols pairs of mothers and neonates (singleton births only) at the East-Limburg Hospital (Genk, Belgium)...
April 2018: Lancet. Planetary Health
https://www.readbyqxmd.com/read/29599129/5-aminoisoquinoline-improves-renal-function-and-fibrosis-during-recovery-phase-of-cisplatin-induced-acute-kidney-injury-in-rats
#10
Andrés Quesada, Francisco O'Valle, Sebastián Montoro-Molina, Mercedes Gómez-Morales, Mercedes Caba-Molina, Juan Francisco González, María C de Gracia, Antonio Osuna, Félix Vargas, Rosemary Wangensteen
The aim of this study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, cisplatin (CisPt) and CisPt+5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg cisplatin, respectively. CisPt+5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 hours before and 24 hours after cisplatin treatment...
March 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29590171/parp1-depletion-induces-rig-i-dependent-signaling-in-human-cancer-cells
#11
Rajib Ghosh, Sanchita Roy, Sonia Franco
DNA Damage Response (DDR) and DNA repair pathways are emerging as potent, ubiquitous suppressors of innate immune signaling in human cells. Here, we show that human cells surviving depletion of the Single Strand Break (SSB) repair protein PARP1 undergo p21-dependent senescence or cell cycle checkpoint activation in the context of activation of innate immune signaling, or viral mimicry. Specifically, we observe induction of a large number of interferon-stimulated genes (ISGs) and multiple pattern recognition receptors (PRRs; including RIG-I, MDA-5, MAVS, TLR3 and STING) and increased nuclear IRF3 staining...
2018: PloS One
https://www.readbyqxmd.com/read/29579711/osthole-inhibits-the-pi3k-akt-signaling-pathway-via-activation-of-pten-and-induces-cell-cycle-arrest-and-apoptosis-in-esophageal-squamous-cell-carcinoma
#12
Xinbing Zhu, Zhengzheng Li, Tongtong Li, Fei Long, Yuesheng Lv, Lei Liu, Xuefeng Liu, Qimin Zhan
Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors and is known to be lack of effective therapy. Thus, novel therapeutic strategies are greatly needed for treatment of ESCC. Osthole, a natural active extract, has been documented to have anti-tumor activity. However, the effect of osthole on ESCC cells has not been elucidated. In this study, we demonstrated that osthole could inhibit the ESCC cell proliferation in dose- and time-dependent manner. Osthole treatment also induced G2/M phase arrest and apoptosis of ESCC cells...
March 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29572258/direct-imaging-of-drug-distribution-and-target-engagement-of-the-parp-inhibitor-rucaparib
#13
Susanne Kossatz, Brandon Carney, Christoper Farley, Charles M Drain, Wolfgang A Weber, Thomas Reiner
PARP inhibitors have emerged as potent anti-tumor drugs. Here, we describe the intrinsic fluorescence properties of the FDA approved PARP inhibitor rucaparib and its potential to directly measure drug distribution and target engagement - a critical factor for understanding drug action and improving efficacy. Methods: We characterized the photophysical properties of rucaparib and determined its quantum yield and lifetime. Using confocal microscopy and flow cytometry, we imaged the intracellular distribution of rucaparib and measured uptake and release kinetics...
March 23, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29572254/parp1-targeted-radiotherapy-in-mouse-models-of-glioblastoma
#14
Stephen A Jannetti, Giuseppe Carlucci, Brandon Carney, Susanne Kossatz, Larissa Shenker, Lukas M Carter, Beatriz Salinas, Christian Brand, Ahmad Sadique, Patrick L Donabedian, Kristen M Cunanan, Mithat Gönen, Vladimir Ponomarev, Brian M Zeglis, Mark M Souweidane, Jason S Lewis, Wolfgang A Weber, John L Humm, Thomas Reiner
The DNA repair enzyme PARP1 is over-expressed in glioblastoma, with overall low expression in healthy brain tissue. Paired with the availability of specific molecularly targeted small molecules for this biomarker, PARP1 is a near-ideal target for novel radiotherapeutics. A successful PARP1-targeted radiotherapeutic would induce DNA damage and apoptosis in cancer cells, while sparing healthy brain tissue. We synthesized a131 I-labeled poly(ADP-ribose) polymerase 1 (PARP1) therapeutic and investigated its pharmacology using in vitro and in vivo methodologies...
March 23, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29570891/poly-adp-ribose-polymerase-1-as-a-potential-therapeutic-target-in-merkel-cell-carcinoma
#15
Renata Ferrarotto, Robert Cardnell, Shirley Su, Lixia Diao, A Karina Eterovic, Victor Prieto, William H Morrisson, Jing Wang, Merrill S Kies, Bonnie S Glisson, Lauren Averett Byers, Diana Bell
BACKGROUND: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma. METHODS: We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples...
March 23, 2018: Head & Neck
https://www.readbyqxmd.com/read/29555554/timeless-is-a-novel-estrogen-receptor-co-activator-involved-in-multiple-signalling-pathways-in-mcf-7-cells
#16
Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of oestrogen receptor α (ERα) stimulates cell division and tumour growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homologue of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
March 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29551729/new-therapeutic-activity-of-metabolic-enhancer-piracetam-in-treatment-of-neurodegenerative-disease-participation-of-caspase-independent-death-factors-oxidative-stress-inflammatory-responses-and-apoptosis
#17
Dinesh Kumar Verma, Sonam Gupta, Joyshree Biswas, Neeraj Joshi, Abhishek Singh, Parul Gupta, Shubhangini Tiwari, K Sivarama Raju, Swati Chaturvedi, M Wahajuddin, Sarika Singh
Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation...
March 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29549427/analysis-of-hpf1-expression-and-function-in-early-embryonic-development-of-zebrafish
#18
Zhen Zhang, Hongwei Sun, Yu Chen, Tianqi Cao, Zhou Songyang, Junjiu Huang, Yan Huang
About 70% of zebrafish (Danio rerio) genes are orthologues of the human's, which are of great interests, but still largely unknown for their functions. Recently, a report on human histone PARylation factor 1 (HPF1/C4orf27) showed that it is involved in DNA damage response along with poly (ADP-ribose) polymerase 1 (PARP1). However, its function in living organism remains unclear. Given that zebrafish has showed its values in modeling human diseases and physiology, we characterized a zebrafish homolog of human HPF1 by sequence alignment...
March 17, 2018: Development Genes and Evolution
https://www.readbyqxmd.com/read/29535829/poly-adp-ribose-polymerase-1-parp1-modifies-ezh2-and-inhibits-ezh2-histone-methyltransferase-activity-after-dna-damage
#19
Lisa B Caruso, Kayla A Martin, Elisabetta Lauretti, Michael Hulse, Micheal Siciliano, Lena N Lupey-Green, Aaron Abraham, Tomasz Skorski, Italo Tempera
The enzyme Poly(ADP-ribose) polymerase 1 (PARP1) plays a very important role in the DNA damage response, but its role in numerous aspects is not fully understood. We recently showed that in the absence of DNA damage, PARP1 regulates the expression of the chromatin-modifying enzyme EZH2. Work from other groups has shown that EZH2 participates in the DNA damage response. These combined data suggest that EZH2 could be a target of PARP1 in both untreated and genotoxic agent-treated conditions. In this work we tested the hypothesis that, in response to DNA damage, PARP1 regulates EZH2 activity...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29534966/next-generation-sequencing-based-mirna-expression-analysis-in-parp1-deficient-embryonic-stem-cell-derived-exosomes
#20
Tadashige Nozaki, Yuka Sasaki, Itsuko Fukuda, Mayu Isumi, Keitaro Nakamoto, Takae Onodera, Mitsuko Masutani
Poly (ADP-ribose) polymerase family, member 1 (Parp1) has pleiotropic and disparate functions in multiple cellular signaling pathways through post-translational protein modification. It contributes to the regulation of various cellular processes, including DNA damage repair, cell death, and cell differentiation, genetically or epigenetically. Meanwhile, the functions of Parp1 in intercellular signaling remain to be established. To examine the functions of Parp1 in intercellular signaling, we examined microRNA (miRNA) regulation in exosomes derived from Parp1-deficient (Parp1-/- ) embryonic stem (ES) cells...
March 10, 2018: Biochemical and Biophysical Research Communications
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