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https://www.readbyqxmd.com/read/29243149/ferulic-acid-protects-against-radiation-induced-testicular-damage-in-male-rats-impact-on-sirt1-and-parp1
#1
Hala O El-Mesallamy, Rania A Gawish, Al-Aliaa M Sallam, Hanan A Fahmy, Ahmed S Nada
Ionizing radiation is a major contributor to male infertility by destroying spermatogenesis. Therefore, the need for an effective radio-protective agent is evident. The objective of the present study was to investigate the potential radio-protective effect of ferulic acid (FA) on radiation-induced testicular damage. Mature male Sprague-Dawley rats were either exposed to a single-dose gamma radiation (5 Gy) and/or treated with FA (50 mg/kg), daily for 7 days before irradiation. Sirtuin1 (SIRT1), poly (ADP-ribose) polymerase 1 (PARP1), cytosolic calcium content, and the male reproductive functions (sperm head abnormality) as well as oxidative stress markers were assessed 7 days after irradiation...
December 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29238179/role-of-poly-adp-ribose-polymerase-1-and-cytokines-in-acute-renal-injury-in-elderly-chinese-patients-with-diabetes-mellitus
#2
Li Cao, Yan Liu, Li Zhang, Yanfei Wei
Objective: The primary objective of this study was to evaluate whether the polymorphism of poly (ADP-ribose) polymerase-1 (PARP-1) is involved as a potential risk factor in the development of acute renal injury in elderly Chinese patients with diabetes mellitus. Subjects and methods: In this pilot study, diabetic patients of either gender (aged ≥65 years) with a confirmed diagnosis of acute renal injury and individuals with no clinical symptoms of acute renal injury were enrolled at Nanxishan Hospital of Guangxi Zhuang Autonomous Region, China...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#3
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29235513/metabolic-engineering-of-the-pentose-phosphate-pathway-for-enhanced-limonene-production-in-the-cyanobacterium-synechocysti-s-sp-pcc-6803
#4
Po-Cheng Lin, Rajib Saha, Fuzhong Zhang, Himadri B Pakrasi
Isoprenoids are diverse natural compounds, which have various applications as pharmaceuticals, fragrances, and solvents. The low yield of isoprenoids in plants makes them difficult for cost-effective production, and chemical synthesis of complex isoprenoids is impractical. Microbial production of isoprenoids has been considered as a promising approach to increase the yield. In this study, we engineered the model cyanobacterium Synechocystis sp. PCC 6803 for sustainable production of a commercially valuable isoprenoid, limonene...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234114/probing-the-requirement-for-cd38-in-retinoic-acid-induced-hl-60-cell-differentiation-with-a-small-molecule-dimerizer-and-genetic-knockout
#5
Robert J MacDonald, Jonathan H Shrimp, Hong Jiang, Lu Zhang, Hening Lin, Andrew Yen
CD38 is an ectoenzyme and receptor with key physiological roles. It metabolizes NAD+ to adenosine diphosphate ribose (ADPR) and cyclic ADPR, regulating several processes including calcium signalling. CD38 is both a positive and negative prognostic indicator in leukaemia. In all-trans retinoic acid (RA)-induced differentiation of acute promyelocytic leukaemia and HL-60 cells, CD38 is one of the earliest and most prominently upregulated proteins known. CD38 overexpression enhances differentiation, while morpholino- and siRNA-induced knockdown diminishes it...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232475/front-line-therapy-of-advanced-ovarian-cancer-new-approaches
#6
J A Ledermann
Background: The 5-year survival of ovarian cancer has slowly increased but to date much of this has been due to the use of more lines of treatment rather than better first-line therapy. In this setting, there has been little improvement over the past 15 years. The introduction of new treatments to extend time to first progression and overall survival remains a key objective of clinical research. Design: The focus of research in the previous decade has been on the incorporation of anti-angiogenic therapy or dose-dense scheduling of paclitaxel (Taxol) to improve outcome...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232465/new-treatments-in-ovarian-cancer
#7
E Pujade-Lauraine
In targeting DNA repair pathways of the most genomic instable cancer, poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) have been demonstrated as the most effective drug since platinum in high grade serous or endometrioid ovarian cancer. Immunotherapy is strongly pushing the door of ovarian cancer and has the ambition to change the fate of this deadly disease when combined with chemotherapy, vascular endothelial growth factor inhibitor or PARPi. The activity of PARPi could also be improved by modulators of the cell cycle, which are required to give time enough for DNA repair...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29231977/dids-inhibits-overexpression-bak1-induced-mitochondrial-apoptosis-through-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway
#8
Xiayun Yang, Shusheng Tang, Daowen Li, Xiaohong Yu, Fuyun Wang, Xilong Xiao
Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29229761/an-unusual-diphosphatase-from-the-phnp-family-cleaves-reactive-fad-photoproducts
#9
Guillaume Aw Beaudoin, Qiang Li, Steven D Bruner, Andrew D Hanson
Flavins are notoriously photolabile, but while the photoproducts derived from the iso -alloxazine ring are well known the other photoproducts are not. In the case of FAD, typically the main cellular flavin, the other photoproducts are predicted to include four- and five-carbon sugars linked to ADP. These FAD photoproducts were shown to be potent glycating agents, more so than ADP-ribose. Such toxic compounds would require disposal via an ADP-sugar diphosphatase or other route. Comparative analysis of bacterial genomes uncovered a candidate disposal gene that is chromosomally clustered with genes for FAD synthesis or transport and is predicted to encode a protein of the PhnP cyclic phosphodiesterase family...
December 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29228718/increased-single-strand-annealing-rather-than-non-homologous-end-joining-predicts-hereditary-ovarian-carcinoma
#10
Miriam Deniz, Tatiana Romashova, Sarah Kostezka, Anke Faul, Theresa Gundelach, Maria Moreno-Villanueva, Wolfgang Janni, Thomas W P Friedl, Lisa Wiesmüller
Mutations in genes encoding DNA double-strand break (DSB) repair components, especially homologous recombination (HR) proteins, were found to predispose to breast and ovarian cancer. Beyond high penetrance risk gene mutations underlying monogenic defects, low risk gene mutations generate polygenic defects, enlarging the fraction of individuals with a predisposing phenotype. DSB repair dysfunction opens new options for targeted therapies; poly (ADP-ribose) polymerase (PARP) inhibitors have been approved for BRCA-mutated and platinum-responsive ovarian cancers...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#11
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29225136/in-vitro-apoptotic-mechanism-of-a-novel-synthetic-quinazolinyl-derivative-induces-caspase-dependent-intrinsic-pathway-on-thp-1-leukemia-cell-line
#12
V Sridhar, S K Arepalli, L R Velatooru, J Venkateswara Rao, P Kavin Kennedy, B Narsaiah
Several quinazoline derivatives have been found to possess a broad spectrum of biological activities. Previously our research group has synthesized and studied the anti-proliferative effects of N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine (DMQA). The current study evaluated the cytotoxic and apoptotic properties of DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A 549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's)...
December 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29223478/phase-ii-trial-of-veliparib-in-patients-with-previously-treated-brca-mutated-pancreas-ductal-adenocarcinoma
#13
Maeve A Lowery, David P Kelsen, Marinela Capanu, Sloane C Smith, Jonathan W Lee, Zsofia K Stadler, Malcolm J Moore, Hedy L Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E Salo-Mullen, Richard Kinh Gian Do, Alice P Chen, Kenneth H Yu, Laura H Tang, Eileen M O'Reilly
PURPOSE: BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC). METHODS: Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled...
December 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29223166/protein-poly-adp-ribosyl-ation-system-changes-in-development-and-aging-as-well-as-due-to-restriction-of-cell-proliferation
#14
REVIEW
G A Shilovsky, S I Shram, G V Morgunova, A N Khokhlov
It is well known that the number of dividing cells in an organism decreases with age. The average rate of cell division in tissues and organs of a mature organism sharply decreases, which is probably a trigger for accumulation of damage leading to disturbance of genome integrity. This can be a cause for the development of many age-related diseases and appearance of phenotypic and physiological signs of aging. In this connection, the protein poly(ADP-ribosyl)ation system, which is activated in response to appearance of various DNA damage, attracts great interest...
November 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29221184/hepatitis-b-virus-x-protein-inhibits-apoptosis-by-modulating-endoplasmic-reticulum-stress-response
#15
Jia Li, Jiang He, Yongming Fu, Xingwang Hu, Lun-Quan Sun, Yan Huang, Xuegong Fan
Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220653/a-poly-adp-ribose-trigger-releases-the-auto-inhibition-of-a-chromatin-remodeling-oncogene
#16
Hari R Singh, Aurelio P Nardozza, Ingvar R Möller, Gunnar Knobloch, Hans A V Kistemaker, Markus Hassler, Nadine Harrer, Charlotte Blessing, Sebastian Eustermann, Christiane Kotthoff, Sébastien Huet, Felix Mueller-Planitz, Dmitri V Filippov, Gyula Timinszky, Kasper D Rand, Andreas G Ladurner
DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29220652/mechanistic-insights-into-autoinhibition-of-the-oncogenic-chromatin-remodeler-alc1
#17
Laura C Lehmann, Graeme Hewitt, Shintaro Aibara, Alexander Leitner, Emil Marklund, Sarah L Maslen, Varun Maturi, Yang Chen, David van der Spoel, J Mark Skehel, Aristidis Moustakas, Simon J Boulton, Sebastian Deindl
Human ALC1 is an oncogene-encoded chromatin-remodeling enzyme required for DNA repair that possesses a poly(ADP-ribose) (PAR)-binding macro domain. Its engagement with PARylated PARP1 activates ALC1 at sites of DNA damage, but the underlying mechanism remains unclear. Here, we establish a dual role for the macro domain in autoinhibition of ALC1 ATPase activity and coupling to nucleosome mobilization. In the absence of DNA damage, an inactive conformation of the ATPase is maintained by juxtaposition of the macro domain against predominantly the C-terminal ATPase lobe through conserved electrostatic interactions...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29217266/auriculasin-induced-ros-causes-prostate-cancer-cell-death-via-induction-of-apoptosis
#18
Hyun-Dong Cho, Ju-Hye Lee, Kwang-Deog Moon, Ki-Hun Park, Mi-Kyung Lee, Kwon-Il Seo
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model...
December 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29216382/improving-crispr-cas-specificity-with-chemical-modifications-in-single-guide-rnas
#19
Daniel E Ryan, David Taussig, Israel Steinfeld, Smruti M Phadnis, Benjamin D Lunstad, Madhurima Singh, Xuan Vuong, Kenji D Okochi, Ryan McCaffrey, Magdalena Olesiak, Subhadeep Roy, Chong Wing Yung, Bo Curry, Jeffrey R Sampson, Laurakay Bruhn, Douglas J Dellinger
CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence') and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays...
December 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29216372/the-c-terminal-domain-of-p53-orchestrates-the-interplay-between-non-covalent-and-covalent-poly-adp-ribosyl-ation-of-p53-by-parp1
#20
Arthur Fischbach, Annika Krüger, Stephanie Hampp, Greta Assmann, Lisa Rank, Matthias Hufnagel, Martin T Stöckl, Jan M F Fischer, Sebastian Veith, Pascal Rossatti, Magdalena Ganz, Elisa Ferrando-May, Andrea Hartwig, Karin Hauser, Lisa Wiesmüller, Alexander Bürkle, Aswin Mangerich
The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions, however, it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate, this study provides detailed insights into the interplay between non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53...
December 4, 2017: Nucleic Acids Research
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