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https://www.readbyqxmd.com/read/28815640/in-vitro-genotoxicity-of-airborne-ni-np-in-air-liquid-interface
#1
Siiri Latvala, Daniel Vare, Hanna L Karlsson, Karine Elihn
Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively...
August 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28807902/h2av-facilitates-h3s10-phosphorylation-but-is-not-required-for-heat-shock-induced-chromatin-decondensation-or-transcriptional-elongation
#2
Yeran Li, Chao Wang, Weili Cai, Saheli Sengupta, Michael Zavortink, Huai Deng, Jack Girton, Jørgen Johansen, Kristen M Johansen
A model has been proposed where JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation to occur. However, here we show that while H3S10 phosphorylation is indeed compromised in the H2Av null mutant we find that chromatin decondensation at heat shock loci is unaffected both in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of Pol II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28804761/unfolding-of-core-nucleosomes-by-parp-1-revealed-by-spfret-microscopy
#3
Daniel C Sultanov, Nadezhda S Gerasimova, Kseniya S Kudryashova, Natalya V Maluchenko, Elena Y Kotova, Marie-France Langelier, John M Pascal, Mikhail P Kirpichnikov, Alexey V Feofanov, Vasily M Studitsky
DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose)polymerase 1) increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer) microscopy...
2017: AIMS Genetics
https://www.readbyqxmd.com/read/28802212/pharmacophore-based-design-of-some-multi-targeted-compounds-targeted-against-pathways-of-diabetic-complications
#4
Navriti Chadha, Om Silakari
Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc...
July 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28801290/-quinalizarin-induces-apoptosis-in-gastric-cancer-ags-cells-via-mapk-and-akt-signaling-pathway
#5
Chang Liu, Ying-Hua Luo, Xian-Ji Piao, Yue Wang, Ling-Qi Meng, Hao Wang, Jia-Ru Wang, Yi Zhang, Jin-Qian Li, Cheng-Hao Jin
OBJECTIVE: To investigate quinalizarin-induced apoptosis in gastric cancer cells in vitro and explore the molecular mechanisms. METHODS: MTT assay was used to determine the cytotoxic effects of quinalizarin on human gastric cancer AGS, MKN-28 and MKN-45 cells. Annexin V-FITC/PI staining and flow cytometry were used to assess quinalizarin-induced apoptosis in AGS cells and its effect on intracellular ROS levels; the expression levels of apoptotic proteins in the cells were determined with Western blotting...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#6
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791810/cytotoxicity-of-anticancer-drugs-and-pj-34-poly-adp-ribose-polymerase-1-parp-1-inhibitor-on-hl-60-and-jurkat-cells
#7
Maciej Stępnik, Sylwia Spryszyńska, Anna Gorzkiewicz, Magdalena Ferlińska
BACKGROUND: The majority of the clinical trials with poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors were conducted or are ongoing in patients with solid tumors, while trials with leukemia patients are less frequent. Surprisingly scarce data is available on the combinatory effects of PARP inhibitors with DNA damaging antitumor drugs in leukemic cells (primary cells or established lines). OBJECTIVES: The aim of the present study was to assess the effect of PJ-34 (PARP-1 inhibitor) on the cytotoxicity of different antileukemic drugs with different DNA damaging mechanisms and potency (doxorubicin, etoposide, cytarabine and chlorambucil) in human leukemic Jurkat and HL-60 cells...
May 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28790837/rucaparib-the-past-present-and-future-of-a-newly-approved-parp-inhibitor-for-ovarian-cancer
#8
REVIEW
L E Dockery, C C Gunderson, K N Moore
Rucaparib camsylate (CO-338, AG-014699, PF-01367338) is a potent PARP-1, PARP-2, and PARP-3 inhibitor. Phase I and II studies demonstrated clinical efficacy in both BRCA-mutated (inclusive of germline and somatic) ovarian tumors and ovarian tumors with homologous recombination deficiency (HRD) loss of heterozygosity (LOH). Rucaparib has received the US Food and Drug Administration (FDA) approval for patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790402/h-ferritin-nanocaged-olaparib-a-promising-choice-for-both-brca-mutated-and-sporadic-triple-negative-breast-cancer
#9
S Mazzucchelli, M Truffi, F Baccarini, M Beretta, L Sorrentino, M Bellini, M A Rizzuto, R Ottria, A Ravelli, P Ciuffreda, D Prosperi, F Corsi
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790198/neutrophil-activation-of-endothelial-cell-expressed-trpm2-mediates-transendothelial-neutrophil-migration-and-vascular-injury
#10
Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M Hecquet, Dheeraj Soni, Jalees Rehman, Chinnaswamy Tiruppathi, Asrar B Malik
Rationale: TRPM2 (Transient Receptor Potential Melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca(2+) entry in response to intracellular generation of adenosine diphosphoribose (ADPR), the TRPM2 ligand. Objective: Because polymorphonuclear leukocytes (PMN) interaction with endothelial cells (ECs) generates ROS, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. Methods and Results: We observed defective PMN transmigration in response to LPS challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2(iΔEC) )...
August 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28777431/involvement-of-poly-adp-ribose-polymerase-1-in-chinese-patients-with-glioma-a-potential-target-for-effective-patient-care
#11
Jinhong Ren, Peilan Jia, Hongxia Feng, Xiuhua Li, Jinghui Zhao, Yunxia Sun
OBJECTIVE: We aimed to evaluate the genetic variation of poly(ADP-ribose) polymerase-1 (PARP-1) in the development of gliomas among Chinese individuals. MATERIALS AND METHODS: Patients with a confirmed diagnosis of glioma and healthy individuals with no clinical symptoms of glioma were enrolled at Liaocheng People's Hospital, China. Genetic polymorphisms were studied in plasma samples by polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine levels were measured routinely in serum samples by sandwich ELISA technique...
July 29, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28767435/the-degradation-of-mixed-lineage-kinase-domain-like-protein-promotes-neuroprotection-after-ischemic-brain-injury
#12
Yanlong Zhou, Beiqun Zhou, Hui Tu, Yan Tang, Chen Xu, Yanbo Chen, Zhong Zhao, Zhigang Miao
Mixed lineage kinase domain-like (MLKL) protein was recently found to play a critical role in necrotic cell death. To explore its role in neurological diseases, we measured MLKL protein expression after ischemia injury in a mouse model. We found that MLKL expression significantly increased 12 h after ischemia/reperfusion (I/R) injury with peak levels at 48 h. Inhibition of MLKL by intraperitoneal administration of NSA significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28763648/design-synthesis-and-biological-evaluation-of-4-amidobenzimidazole-acridine-derivatives-as-dual-parp-and-topo-inhibitors-for-cancer-therapy
#13
Zigao Yuan, Shaopeng Chen, Changjun Chen, Jiwei Chen, Chengken Chen, Qiuzi Dai, Chunmei Gao, Yuyang Jiang
PARP-1 could repair the DNA damages induced by Topo inhibitors, therefore inhibiting Topo and PARP-1 simultaneously might be able to overcome resistance and improve outcomes. In this study a series of 4-amidobenzimidazole acridines were designed and synthesized as dual Topo and PARP-1 inhibitors. Compound 11l displayed good inhibitory activities against Topo and PARP-1, as well as significantly inhibited cancer cells proliferation. Further mechanistic evaluations indicated that 11l treatment in MCF-7 cells induced accumulated DNA double-strand breaks, prompted remarkable apoptosis, and caused prominent G0/G1 cell cycle arrest...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28759041/oncosis-and-apoptosis-induction-by-activation-of-an-overexpressed-ion-channel-in-breast-cancer-cells
#14
A A Peters, S Y N Jamaludin, K T D S Yapa, S Chalmers, A P Wiegmans, H F Lim, M J G Milevskiy, I Azimi, F M Davis, K S Northwood, E Pera, D L Marcial, E Dray, N J Waterhouse, P J Cabot, T J Gonda, P A Kenny, M A Brown, K K Khanna, S J Roberts-Thomson, G R Monteith
The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28757444/possible-role-of-papr-1-in-protecting-human-hacat-cells-against-cytotoxicity-of-sio2-nano
#15
Chunmei Gong, Linqing Yang, Jichang Zhou, Guo Xiang, Zhixiong Zhuang
Nano-SiO2 materials play a significant role in the engineered nanomaterials (ENMs) field. The ease of their production as well as their relatively low cost has promoted the wide use of these products in many fields. Nano-SiO2 exposure is known to cause severe DNA damage; however, the underlying mechanisms remain poorly understood. In a previous study, we found that nano-SiO2 exposure regulate the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells. Here, we employed lentivirus-mediated RNA interference (RNAi) to knock down PAPR-1 expression in HaCaT cells and explored the potential role of PARP-1 in nano-SiO2 induced cytotoxicity...
July 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28756616/parp-1-par-activity-in-cultured-human-lens-epithelial-cells-exposed-to-two-levels-of-uvb-light
#16
Caroline S Cencer, Shravan K Chintala, Tenira J Townsend, Daniel P Feldmann, Mirna A Awrow, Nahrain A Putris, Mason E Geno, Maria G Donovan, Frank J Giblin
This study investigated poly (ADP-ribose) polymerase-1 (PARP-1) activation in cultured human lens epithelial cells exposed to two levels of UVB light (312 nm peak wavelength), 0.014 and 0.14 J/cm(2) ("low" and "high" dose, respectively). At the low dose, PARP-1 and poly (ADP-ribose) (PAR) polymers acted to repair DNA strand breaks rapidly with no subsequent major effects on either cell morphology or viability. However, following the high UVB dose, there was a dramatic second phase of PARP-1 activation, 90 min later, which included a sudden reappearance of DNA strand breaks, bursts of reactive oxygen species (ROS) formation both within the mitochondria and nucleus, a translocation of PAR from the nucleus to the mitochondria, and an ultimate 70% loss of cell viability occurring after 24 hrs...
July 30, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28751918/cellular-responses-in-human-dental-pulp-stem-cells-treated-with-three-endodontic-materials
#17
Alejandro Victoria-Escandell, José Santiago Ibañez-Cabellos, Sergio Bañuls-Sánchez de Cutanda, Ester Berenguer-Pascual, Jesús Beltrán-García, Eva García-López, Federico V Pallardó, José Luis García-Giménez, Antonio Pallarés-Sabater, Ignacio Zarzosa-López, Manuel Monterde
Human dental pulp stem cells (HDPSCs) are of special relevance in future regenerative dental therapies. Characterizing cytotoxicity and genotoxicity produced by endodontic materials is required to evaluate the potential for regeneration of injured tissues in future strategies combining regenerative and root canal therapies. This study explores the cytotoxicity and genotoxicity mediated by oxidative stress of three endodontic materials that are widely used on HDPSCs: a mineral trioxide aggregate (MTA-Angelus white), an epoxy resin sealant (AH-Plus cement), and an MTA-based cement sealer (MTA-Fillapex)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28733611/integrin-%C3%AE-6%C3%AE-4-upregulates-amphiregulin-and-epiregulin-through-base-excision-repair-mediated-dna-demethylation-and-promotes-genome-wide-dna-hypomethylation
#18
Brittany L Carpenter, Jinpeng Liu, Lei Qi, Chi Wang, Kathleen L O'Connor
Aberrant DNA methylation patterns are a common theme across all cancer types. Specific DNA demethylation of regulatory sequences can result in upregulation of genes that are critical for tumor development and progression. Integrin α6β4 is highly expressed in pancreatic carcinoma and contributes to cancer progression, in part, through the specific DNA demethylation and upregulation of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG). Whole genome bisulfite sequencing (WGBS) revealed that integrin α6β4 signaling promotes an overall hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal promoters of AREG and EREG...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731097/dba-induced-caspase-3-dependent-apoptosis-occurs-through-mitochondrial-translocation-of-cyt-c-in-the-rat-hippocampus
#19
Wenbo Jiang, Yingying Chen, Bai Li, Shuying Gao
Dibromoacetic acid (DBA), a by-product of disinfection, develops in drinking water during chlorination or ozonation processes. Water intake is the main source of DBA exposure in humans, which is potentially neurotoxic. The present study investigated the neurotoxic effects of DBA by assessing the behavioral and biochemical characteristics of Sprague Dawley rats intragastrically treated with DBA at concentrations of 20, 50 and 125 mg kg(-1) body weight for 28 consecutive days. The results indicated that animal weight gain and food consumption were not significantly affected by DBA...
July 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28719017/contrasting-sirtuin-and-parp-activity-of-selected-2-4-6-trisubstituted-benzimidazoles
#20
Keng Yoon Yeong, Soo Choon Tan, Chun-Wai Mai, Chee-Onn Leong, Felicia Fei-Lei Chung, Yean Kee Lee, Chin Fei Chee, Noorsaadah Abdul Rahman
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activity. We showed that modification on benzimidazoles may alter their selectivity towards sirtuin or PARP-1 enzymes...
July 18, 2017: Chemical Biology & Drug Design
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