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https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#1
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28503382/poly-adp-ribosylation-is-present-in-murine-sciatic-nerve-fibers-and-is-altered-in-a-charcot-marie-tooth-1e-neurodegenerative-model
#2
Laura I Lafon Hughes, Carlos J Romeo Cardeillac, Karina B Cal Castillo, Salomé C Vilchez Larrea, José R Sotelo Sosa, Gustavo A Folle Ungo, Silvia H Fernández Villamil, Alejandra E Kun González
BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28415460/poly-arginine-graphene-quantum-dots-as-a-biocompatible-and-non-toxic-nanocomposite-layer-by-layer-electrochemical-preparation-characterization-and-non-invasive-malondialdehyde-sensory-application-in-exhaled-breath-condensate
#3
Mohammad Hasanzadeh, Fozieh Mokhtari, Nasrin Shadjou, Aziz Eftekhari, Ahad Mokhtarzadeh, Vahid Jouyban-Gharamaleki, Soltanali Mahboob
This study reports on the electropolymerization of a low toxic and biocompatible polymer with entitle poly arginine-graphene quantum dots (PARG-GQDs) as a novel strategy for surface modification of glassy carbon (GC) surface and preparation a new interface for biomedical application. The fabrication of PARG-GQDs on GCE was performed using Layer-by-layer regime. Scanning electron microscopy (SEM) was confirmed dispersion of GQDs on the surface of PARG which lead to increase of surface coverage of PARG. The redox behavior of prepared sensor was then characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CHA), square wave voltammetry (SWV), linear sweep voltammetry (LSV)...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28254358/specific-killing-of-dna-damage-response-deficient-cells-with-inhibitors-of-poly-adp-ribose-glycohydrolase
#4
Polly Gravells, Emma Grant, Kate M Smith, Dominic I James, Helen E Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks...
April 2017: DNA Repair
https://www.readbyqxmd.com/read/28235590/rational-design-of-polyarginine-nanocapsules-intended-to-help-peptides-overcoming-intestinal-barriers
#5
Zhigao Niu, Erik Tedesco, Federico Benetti, Aloïse Mabondzo, Isabella Monia Montagner, Ilaria Marigo, David Gonzalez-Touceda, Sulay Tovar, Carlos Diéguez, Manuel J Santander-Ortega, María J Alonso
The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80...
February 21, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28144953/the-rhce-ce-501a-allele-encodes-the-parg-antigen-rh60
#6
Erwin A Scharberg, Gabi Rink, Sabine Roth, Susanne Seyboth, Ekkehard Richter, Birgit S Gathof, Jürgen Burkhart, Peter Bugert
No abstract text is available yet for this article.
January 31, 2017: Transfusion
https://www.readbyqxmd.com/read/28069389/layer-by-layer-assembly-of-hierarchical-nanoarchitectures-to-enhance-the-systemic-performance-of-nanoparticle-albumin-bound-paclitaxel
#7
Hima Bindu Ruttala, Thiruganesh Ramasamy, Beom Soo Shin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Although protein-bound paclitaxel (PTX, Abraxane(®)) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer (LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly (L-aspartic acid) (PEG-b-PLD) onto an albumin conjugate...
March 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28034957/a-three-dimensional-parf-meshwork-assembles-through-the-nucleoid-to-mediate-plasmid-segregation
#8
Brett N McLeod, Gina E Allison-Gamble, Madhuri T Barge, Nam K Tonthat, Maria A Schumacher, Finbarr Hayes, Daniela Barillà
Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#9
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
February 2017: Pathology
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#10
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27855960/polyarginine-nanocapsules-as-a-potential-oral-peptide-delivery-carrier
#11
Giovanna Lollo, Ana Gonzalez-Paredes, Marcos Garcia-Fuentes, Pilar Calvo, Dolores Torres, Maria Jose Alonso
We have previously reported the development of novel nanocapsules made of polyarginine (PArg) specifically designed for the delivery of small anticancer drugs into cells. Our goal, in this work, has been to investigate the potential of these nanocarriers for oral delivery of peptide anticancer drugs. To reach this objective, we chose the antitumoral peptide, elisidepsin, and evaluated the characteristics of the PArg nanocapsules in terms of drug loading capacity, stability in simulated intestinal fluids, and ability to interact with the intestinal epithelium both in vitro (Caco-2 model cell line) and in vivo...
February 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27817743/new-insights-into-the-roles-of-nad-poly-adp-ribose-metabolism-and-poly-adp-ribose-glycohydrolase
#12
REVIEW
Seiichi Tanuma, Akira Sato, Takahiro Oyama, Atsushi Yoshimori, Hideaki Abe, Fumiaki Uchiumi
Accumulating evidence has suggested the fundamental functions of NAD+-poly(ADP-ribose) metabolism in cellular and physiological processes, including energy homeostasis, signal transduction, DNA transaction, genomic stability and cell death or survival. The NAD+ biosynthesis and poly(ADP-ribose) [(ADP-R)n] turnover are tightly controlled by several key enzymes, such as nicotinamide phosphoribosyltransferase (NmPRT), nicotinamide mononucleotide adenylyltransferases (NMNATs), poly(ADP-ribose) polymerase (PARP), poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribose pyrophosphorylase (ADPRPPL)...
2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27817742/parg-inhibitors-and-functional-parg-inhibition-models
#13
Yuka Sasaki, Miyuki Hozumi, Hiroaki Fujimori, Yasufumi Murakami, Fumiaki Koizumi, Kengo Inoue, Mitsuko Masutani
Poly(ADP-ribose) polymerases (PARPs) family proteins catalyze poly(ADP-ribosylation) (PARylation) by conjugating ADP-ribose residues repeatedly on amino acid residues using nicotinamide adenine dinucleotide as a substrate. The inhibitors of PARP widely block DNA repair processes and are currently examined in clinical trials of cancer therapy. Poly(ADP-ribose) glycohydrolase (PARG) is the main nuclear enzyme, which digests poly(ADP-ribose) into ADP-ribose. PARG inhibitor could also be considered as a chemotherapeutic agent for cancer, because of its involvement in DNA repair...
2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27749819/arginine-phosphorylation-marks-proteins-for-degradation-by-a-clp-protease
#14
Débora Broch Trentini, Marcin Józef Suskiewicz, Alexander Heuck, Robert Kurzbauer, Luiza Deszcz, Karl Mechtler, Tim Clausen
Protein turnover is a tightly controlled process that is crucial for the removal of aberrant polypeptides and for cellular signalling. Whereas ubiquitin marks eukaryotic proteins for proteasomal degradation, a general tagging system for the equivalent bacterial Clp proteases is not known. Here we describe the targeting mechanism of the ClpC-ClpP proteolytic complex from Bacillus subtilis. Quantitative affinity proteomics using a ClpP-trapping mutant show that proteins phosphorylated on arginine residues are selectively targeted to ClpC-ClpP...
November 3, 2016: Nature
https://www.readbyqxmd.com/read/27697151/inhibiting-poly-adp-ribosylation-improves-axon-regeneration
#15
Alexandra B Byrne, Rebecca D McWhirter, Yuichi Sekine, Stephen M Strittmatter, David M Miller, Marc Hammarlund
The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C...
October 4, 2016: ELife
https://www.readbyqxmd.com/read/27689388/first-in-class-chemical-probes-against-poly-adp-ribose-glycohydrolase-parg-inhibit-dna-repair-with-differential-pharmacology-to-olaparib
#16
Dominic I James, Kate M Smith, Allan M Jordan, Emma E Fairweather, Louise A Griffiths, Nicola S Hamilton, James R Hitchin, Colin P Hutton, Stuart Jones, Paul Kelly, Alison E McGonagle, Helen Small, Alexandra I J Stowell, Julie Tucker, Ian D Waddell, Bohdan Waszkowycz, Donald J Ogilvie
The enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). However, a detailed understanding of its mechanism of action has been hampered by a lack of credible, cell-active chemical probes. Herein, we demonstrate inhibition of PARG with a small molecule, leading to poly(ADP-ribose) (PAR) chain persistence in intact cells. Moreover, we describe two advanced, and chemically distinct, cell-active tool compounds with convincing on-target pharmacology and selectivity...
November 18, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27610220/an-assay-to-measure-poly-adp-ribose-glycohydrolase-parg-activity-in-cells
#17
Dominic I James, Stephen Durant, Kay Eckersley, Emma Fairweather, Louise A Griffiths, Nicola Hamilton, Paul Kelly, Mark O'Connor, Kerry Shea, Ian D Waddell, Donald J Ogilvie
After a DNA damage signal multiple polymers of ADP ribose attached to poly(ADP) ribose (PAR) polymerases (PARPs) are broken down by the enzyme poly(ADP) ribose glycohydrolase (PARG). Inhibition of PARG leads to a failure of DNA repair and small molecule inhibition of PARG has been a goal for many years. To determine whether biochemical inhibitors of PARG are active in cells we have designed an immunofluorescence assay to detect nuclear PAR after DNA damage. This 384-well assay is suitable for medium throughput high-content screening and can detect cell-permeable inhibitors of PARG from nM to µM potency...
2016: F1000Research
https://www.readbyqxmd.com/read/27544639/y-box-binding-protein-1-as-a-non-canonical-factor-of-base-excision-repair
#18
Elizaveta E Alemasova, Nina A Moor, Konstantin N Naumenko, Mikhail M Kutuzov, Maria V Sukhanova, Pavel E Pestryakov, Olga I Lavrik
Base excision repair (BER) is a flagship DNA repair system responsible for maintaining genome integrity. Apart from basal enzymes, this system involves several accessory factors essential for coordination and regulation of DNA processing during substrate channeling. Y-box-binding protein 1 (YB-1), a multifunctional factor that can interact with DNA, RNA, poly(ADP-ribose) and plenty of proteins including DNA repair enzymes, is increasingly considered as a non-canonical protein of BER. Here we provide quantitative characterization of YB-1 physical interactions with key BER factors such as PARP1, PARP2, APE1, NEIL1 and pol β and comparison of the full-length YB-1 and its C-terminally truncated nuclear form in regard to their binding affinities for BER proteins...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27518087/cd38-knockout-mice-show-significant-protection-against-ischemic-brain-damage-despite-high-level-poly-adp-ribosylation
#19
Aaron Long, Ji H Park, Nina Klimova, Carol Fowler, David J Loane, Tibor Kristian
Several enzymes in cellular bioenergetics metabolism require NAD(+) as an essential cofactor for their activity. NAD(+) depletion following ischemic insult can result in cell death and has been associated with over-activation of poly-ADP-ribose polymerase PARP1 as well as an increase in NAD(+) consuming enzyme CD38. CD38 is an NAD(+) glycohydrolase that plays an important role in inflammatory responses. To determine the contribution of CD38 activity to the mechanisms of post-ischemic brain damage we subjected CD38 knockout (CD38KO) mice and wild-type (WT) mice to transient forebrain ischemia...
January 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27471034/poly-adp-ribose-polymerases-covalently-modify-strand-break-termini-in-dna-fragments-in-vitro
#20
Ibtissam Talhaoui, Natalia A Lebedeva, Gabriella Zarkovic, Christine Saint-Pierre, Mikhail M Kutuzov, Maria V Sukhanova, Bakhyt T Matkarimov, Didier Gasparutto, Murat K Saparbaev, Olga I Lavrik, Alexander A Ishchenko
Poly(ADP-ribose) polymerases (PARPs/ARTDs) use nicotinamide adenine dinucleotide (NAD(+)) to catalyse the synthesis of a long branched poly(ADP-ribose) polymer (PAR) attached to the acceptor amino acid residues of nuclear proteins. PARPs act on single- and double-stranded DNA breaks by recruiting DNA repair factors. Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3'-cordycepin, 5'- and 3'-phosphate and also to 5'-phosphate of a single-stranded oligonucleotide...
July 28, 2016: Nucleic Acids Research
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