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https://www.readbyqxmd.com/read/28819918/network-analysis-of-se-and-zn-related-proteins-in-the-serum-proteomics-expression-profile-of-the-endemic-dilated-cardiomyopathy-keshan-disease
#1
Sen Wang, Yanyan Lv, Yingting Wang, Peiru Du, Wuhong Tan, Mikko J Lammi, Xiong Guo
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples...
August 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28808049/the-1q42-1-risk-allele-promotes-melanoma-via-parp1-upregulation
#2
(no author information available yet)
An intronic indel variant enhances RECQL binding to upregulate PARP1 in melanocytic cells.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28806493/olaparib-a-clinically-used-poly-adp-ribose-polymerase-inhibitor-protects-against-oxidant-induced-cardiac-myocyte-death-in-vitro-and-improves-cardiac-contractility-during-early-phase-after-heart-transplantation-in-a-rat-model-in-vivo
#3
Sevil Korkmaz-Icöz, Bartosz Szczesny, Michela Marcatti, Shiliang Li, Mihály Ruppert, Felix Lasitschka, Sivakkanan Loganathan, Csaba Szabo, Gábor Szabó
BACKGROUND AND PURPOSE: Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) have recently been approved for human use for oncological indications. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effect of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in-vivo model of cardiac transplantation. EXPERIMENTAL APPROACH: H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen-peroxide (H2 O2 ) or with glucose-oxidase (GOx, which generates H2 O2 in the tissue culture medium)...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28805810/trf2-binds-branched-dna-to-safeguard-telomere-integrity
#4
Isabelle Schmutz, Leonid Timashev, Wei Xie, Dinshaw J Patel, Titia de Lange
Although t-loops protect telomeres, they are at risk of cleavage by Holliday junction (HJ) resolvases if branch migration converts the three-way t-loop junction into four-way HJs. T-loop cleavage is repressed by the TRF2 basic domain, which binds three- and four-way junctions and protects HJs in vitro. By replacing the basic domain with bacterial-protein domains binding three- and four-way junctions, we demonstrated the in vivo relevance of branched-DNA binding. Branched-DNA binding also repressed PARP1, presumably by masking the PARP1 site in the t-loop junction...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28802254/tdp1-is-critical-for-the-repair-of-dna-breaks-induced-by-sapacitabine-a-nucleoside-also-targeting-atm-and-brca-deficient-tumors
#5
Muthana Al Abo, Hiroyuki Sasanuma, Xiaojun Liu, Vinodh N Rajapakse, Shar-Yin N Huang, Evgeny Kiselev, Shunichi Takeda, William Plunkett, Yves Pommier
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28801318/from-dna-binding-to-transcriptional-activation-is-the-tale-complete
#6
Nicoletta Bobola
How transcription factors (TFs) control enhancer and promoter functions to effect changes in gene expression is an important question. In this issue, Hau et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701154) show that the TALE TF MEIS recruits the histone modifier PARP1/ARTD1 at promoters to decompact chromatin and activate transcription.
August 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28795251/5-fluorouracil-induced-mitochondrial-oxidative-cytotoxicity-and-apoptosis-are-increased-in-mcf-7-human-breast-cancer-cells-by-trpv1-channel-activation-but-not-hypericum-perforatum-treatment
#7
Haci Ahmet Deveci, Mustafa Nazıroğlu, Gökhan Nur
5-Fluorouracil (5-FU) is a widely used chemotherapy agent for breast cancer, although drug resistance is a critical issue regarding the use of this agent in the disease. Calcium signaling is a well-known main cause of proliferation and apoptosis in breast cancer cells. Although previous studies have implicated TRPV1 inhibitor, anticancer, and apoptotic roles of Hypericum perforatum (HPer) in several cells, the synergistic inhibition effects of HPer and 5-FU in cancer and the stimulation of ongoing apoptosis have not yet been clarified in MCF-7 cells...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28770827/discovery-of-potent-2-4-difluoro-linker-poly-adp-ribose-polymerase-1-inhibitors-with-enhanced-water-solubility-and-in-vivo-anticancer-efficacy
#8
Wen-Hua Chen, Shan-Shan Song, Ming-Hui Qi, Xia-Juan Huan, Ying-Qing Wang, Hualiang Jiang, Jian Ding, Guo-Bin Ren, Ze-Hong Miao, Jian Li
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, we identified a series of 2,4-difluorophenyl-linker analogs (15-55) derived from olaparib as novel PARP1 inhibitors. Four potent analogs 17, 43, 47, and 50 (IC50=2.2-4.4 nmol/L) effectively inhibited the proliferation of Chinese hamster lung fibroblast V-C8 cells (IC50=3...
August 3, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28767699/molecular-evolutionary-patterns-of-nad-sirtuin-aging-signaling-pathway-across-taxa
#9
Uma Gaur, Jianbo Tu, Diyan Li, Yue Gao, Ting Lian, Boyuan Sun, Deying Yang, Xiaolan Fan, Mingyao Yang
A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance...
2017: PloS One
https://www.readbyqxmd.com/read/28767438/nherf1-together-with-parp1-and-brca1-expression-as-a-new-potential-biomarker-to-stratify-breast-cancer-patients
#10
Anita Mangia, Emanuela Scarpi, Giulia Partipilo, Laura Schirosi, Giuseppina Opinto, Francesco Giotta, Giovanni Simone
It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs)...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28767436/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#11
Guang-Yu Bai, Si-Hang Song, Rui-Zhen Sun, Zi-Hui Zhang, Jingyu Li, Zhen-Dong Wang, Zhong-Hua Liu, Lei Lei
Somatic cell nuclear transfer is an important technique for life science research, but its efficiency is still extremely low, and most genes that are important during early development, such as X chromosome-linked genes, are not appropriately expressed during this process. Poly (ADP-ribose) polymerase (PARP) is an enzyme that transfers ADP ribose clusters to target proteins. PARP family members such as PARP1 participate in cellular signalling pathways through poly (ADP-ribosylation) (PARylation), which ultimately promotes changes in chromatin structure, gene expression, and the localization and activity of proteins that mediate signalling responses...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765909/attenuation-of-muc4-potentiates-the-anticancer-activity-of-auranofin-via-regulation-of-the-her2-akt-foxo3-pathway-in-ovarian-cancer-cells
#12
Jun Sang Bae, Jongsung Lee, Yoonkook Park, Kyungmoon Park, Jung Ryul Kim, Dong Hyu Cho, Kyu Yun Jang, See-Hyoung Park
Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28760956/poly-adp-ribose-polymerase-1-escorts-xpc-to-uv-induced-dna-lesions-during-nucleotide-excision-repair
#13
Mihaela Robu, Rashmi G Shah, Nupur K Purohit, Pengbo Zhou, Hanspeter Naegeli, Girish M Shah
Xeroderma pigmentosum C (XPC) protein initiates the global genomic subpathway of nucleotide excision repair (GG-NER) for removal of UV-induced direct photolesions from genomic DNA. The XPC has an inherent capacity to identify and stabilize at the DNA lesion sites, and this function is facilitated in the genomic context by UV-damaged DNA-binding protein 2 (DDB2), which is part of a multiprotein UV-DDB ubiquitin ligase complex. The nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) has been shown to facilitate the lesion recognition step of GG-NER via its interaction with DDB2 at the lesion site...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28759753/inhibition-of-rad51-sensitizes-breast-cancer-cells-with-wild-type-pten-to-olaparib
#14
Qian Zhao, Jiawei Guan, Zhiwei Zhang, Jian Lv, Yulu Wang, Likun Liu, Qi Zhou, Weifeng Mao
PTEN is a tumor suppressor gene well characterized as a phosphatase. However, more evidences demonstrate PTEN functions in DNA repair independent of its phosphatase activity, which affects the efficacy of DNA damage anti-tumoral drugs in treating cancer cells with PTEN variations. Using BT549 breast cancer cells, we studied the roles of PTEN in DNA repair and in sensitization of breast cancer cells to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. Comet assay showed PTEN promoted DNA repair. PTEN-deficient BT549 cells are sensitive to olaparib, which shows the synthetic lethality between PTEN and PARP1...
July 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28759004/a-common-intronic-variant-of-parp1-confers-melanoma-risk-and-mediates-melanocyte-growth-via-regulation-of-mitf
#15
Jiyeon Choi, Mai Xu, Matthew M Makowski, Tongwu Zhang, Matthew H Law, Michael A Kovacs, Anton Granzhan, Wendy J Kim, Hemang Parikh, Michael Gartside, Jeffrey M Trent, Marie-Paule Teulade-Fichou, Mark M Iles, Julia A Newton-Bishop, D Timothy Bishop, Stuart MacGregor, Nicholas K Hayward, Michiel Vermeulen, Kevin M Brown
Previous genome-wide association studies have identified a melanoma-associated locus at 1q42.1 that encompasses a ∼100-kb region spanning the PARP1 gene. Expression quantitative trait locus (eQTL) analysis in multiple cell types of the melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk allele (rs3219090[G]) is correlated with higher PARP1 levels. In silico fine-mapping and functional validation identified a common intronic indel, rs144361550 (-/GGGCCC; r(2) = 0.947 with rs3219090), as displaying allele-specific transcriptional activity...
July 31, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28756530/intricatinol-synergistically-enhances-the-anticancerous-activity-of-cisplatin-in-human-a549-cells-via-p38-mapk-p53-signalling
#16
Vipendra Kumar Singh, Deepika Arora, Neeraj Kumar Satija, Puneet Khare, Somendu Kumar Roy, Pradeep Kumar Sharma
Platinum containing drugs are widely used to treat advanced lung carcinomas. However, their clinical success is still limited due to severe side effects, and drug resistance. Alternative approaches are warranted to augment efficacy of platinum based chemotherapeutic drugs with minimal side effects. Intricatinol (INT), a homoisoflavonoid, has been shown to possess anti-tubercular, antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer activity largely remains unknown. In the present study, we have evaluated anticancer potential of INT alone or in combination with cisplatin (CIS) in non-small cell lung carcinoma (A549) cells...
July 29, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28756516/synthetic-lethality-in-malignant-pleural-mesothelioma-with-parp1-inhibition
#17
Gayathri Srinivasan, Gurjit Singh Sidhu, Elizabeth A Williamson, Aruna S Jaiswal, Nasreen Najmunnisa, Keith Wilcoxen, Dennie Jones, Thomas J George, Robert Hromas
Malignant pleural mesotheliomas (MPM) are most often surgically unresectable, and they respond poorly to current chemotherapy and radiation therapy. Between 23 and 64% of malignant pleural mesothelioma have somatic inactivating mutations in the BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for survival, similar to the BRCA1/2 mutant breast and ovarian cancers...
July 29, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28754563/changes-in-gene-expression-variability-reveal-a-stable-synthetic-lethal-interaction-network-in-brca2-ovarian-cancers
#18
Raymund Bueno, Jessica C Mar
Synthetic lethal interactions (SLIs) are robust mechanisms that provide cells with the ability to sustain viability despite having mutations in genes critical to the DNA damage response, a core cellular process. Studies in model organisms such as S. cerevisiae showed that thousands of genes important in maintaining DNA integrity cooperated in a SLI network. Two genes participate in a SLI when mutation in one gene has no effect on the cell, but mutations in both interacting genes are lethal. Furthermore in C...
July 25, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28751718/two-mouse-models-reveal-an-actionable-parp1-dependence-in-aggressive-chronic-lymphocytic-leukemia
#19
Gero Knittel, Tim Rehkämper, Darya Korovkina, Paul Liedgens, Christian Fritz, Alessandro Torgovnick, Yussor Al-Baldawi, Mona Al-Maarri, Yupeng Cun, Oleg Fedorchenko, Arina Riabinska, Filippo Beleggia, Phuong-Hien Nguyen, F Thomas Wunderlich, Monika Ortmann, Manuel Montesinos-Rongen, Eugen Tausch, Stephan Stilgenbauer, Lukas P Frenzel, Marco Herling, Carmen Herling, Jasmin Bahlo, Michael Hallek, Martin Peifer, Reinhard Buettner, Thorsten Persigehl, H Christian Reinhardt
Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent cytogenetic aberrations, namely del(17p), affecting TP53, and del(11q), affecting ATM, are associated with resistance against genotoxic chemotherapy (del17p) and poor outcome (del11q and del17p). Both del(17p) and del(11q) are also associated with inferior outcome to the novel targeted agents, such as the BTK inhibitor ibrutinib. Thus, even in the era of targeted therapies, CLL with alterations in the ATM/p53 pathway remains a clinical challenge...
July 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28751426/parp2-deficiency-affects-invariant-nkt-cell-maturation-and-protects-mice-from-concanavalin-a-induced-liver-injury
#20
Aveline Filliol, Claire Piquet-Pellorce, Sarah Dion, Valentine Genet, Catherine Lucas-Clerc, Françoise Dantzer, Michel Samson
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during Concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells which promote inflammation and induce hepatocyte death, mediated by the activated invariant NKT-(iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs such as spleen, thymus, and bone marrow in Parp2 deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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