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https://www.readbyqxmd.com/read/29679279/role-of-inositol-polyphosphates-in-programed-cell-death-in-dictyostelium-discoideum-and-its-developmental-life-cycle
#1
Qudes Al-Anbaky, Zeiyad Al-Karakooly, Richard Connor, Lisa Williams, Azure Yarbrough, John Bush, Nawab Ali
Programed cell death or apoptosis is a key developmental process that maintains tissue homeostasis in multicellular organisms. Inositol polyphosphates (InsPs) are key signaling molecules known to regulate a variety of cellular processes including apoptosis in such organisms. The signaling role of InsPs in unicellular organisms such as Dictyostelium discoideum (D. discoideum) is not well understood. We investigated whether InsPs also play any role in apoptosis in D. discoideum and whether InsPs-mediated apoptosis follows a mechanism similar to that present in higher multicellular eukaryotes...
April 20, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29678570/overexpression-of-nrk1-ameliorates-diet-and-age-induced-hepatic-steatosis-and-insulin-resistance
#2
Rui Fan, Jing Cui, Feng Ren, Qingzhi Wang, Yanmei Huang, Bin Zhao, Lai Wei, Xinlai Qian, Xiwen Xiong
NAD+ is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including Sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD+ biosynthesis and lipid metabolism...
April 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29676938/the-development-of-a-biotinylated-nad-applied-human-poly-adp-ribose-polymerase-3-parp3-enzymatic-assay
#3
Ming Ji, Liyuan Wang, Nina Xue, Fangfang Lai, Sen Zhang, Jing Jin, Xiaoguang Chen
Poly(ADP-ribose) polymerase 3 (PARP3) is an important member of the PARP family and shares high structural similarities with both PARP1 and PARP2. The biological roles of PARP3 are currently under investigation; however, several key reports indicate the integral roles of PARP3 in DNA damage repair, and thus it has been investigated as a novel target in oncology. It is clear that the identification of selective PARP3 inhibitors would further advance the understanding of the biological roles of PARP3. Herein, we describe a modified PARP3 screening assay using biotinylated NAD+ as the specialized substrate...
April 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#4
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29671785/activation-of-er-stress-dependent-mir-216b-has-a-critical-role-in-salvia-miltiorrhiza-ethanol-extract-induced-apoptosis-in-u266-and-u937-cells
#5
Changmin Kim, Hyo-Sook Song, Hojung Park, Bonglee Kim
Although Salvia miltiorrhiza has been reported to have anti-cancer mechanisms, such as caspase activation, cell cycle arrest, an anti-angiogenesis effect, and Bcl-2 family regulation, its underlying mechanism of endoplasmic reticulum (ER) stress-mediated apoptosis has never been demonstrated. Thus, in this current study, ER stress-related apoptosis via miR-216b of the ethanol extract of Salvia miltiorrhiza (SM) is elucidated for the first time. SM treatment inhibited the viability of U266 and U937 cells in a concentration-dependent manner...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670377/crocin-induces-autophagic-apoptosis-in-hepatocellular-carcinoma-by-inhibiting-akt-mtor-activity
#6
Chong Yao, Bing-Bing Liu, Xiao-Dong Qian, Li-Qin Li, Heng-Bin Cao, Qiao-Sheng Guo, Gui-Fen Zhou
Background: Autophagy induction is a common mechanism for antitumor chemicals in induction of cancer cell death. However, the role of autophagy in crocin-induced apoptosis is barely studied in hepatocellular carcinoma (HCC). Materials and methods: The influence of crocin on growth, apoptosis, and autophagy and its mutual relations were analyzed by Cell Counting Kit-8 assay, flow cytometer, EGFP-LC3 puncta analysis, and Western blot in HCC cells. The activities of Akt/mTOR axis and its roles in autophagy regulation were also detected by Western blot in HCC cells treated with crocin...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29670134/detection-of-functional-protein-domains-by-unbiased-genome-wide-forward-genetic-screening
#7
Mareike Herzog, Fabio Puddu, Julia Coates, Nicola Geisler, Josep V Forment, Stephen P Jackson
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies to identify mechanisms of drug resistance, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations has been limited. Here, by demonstrating its utility in identifying chemical-genetic suppressors of sensitivity to the DNA topoisomerase I poison camptothecin or the poly(ADP-ribose) polymerase inhibitor olaparib, we detail an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast or haploid mammalian cells in a short timeframe, and with potential applications in other haploid systems...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669812/tankyrase-modulates-insulin-sensitivity-in-skeletal-muscle-cells-by-regulating-the-stability-of-glut4-vesicle-proteins
#8
Zhiduan Su, Vinita Deshpande, David E James, Jacqueline Stöckli
Tankyrase1 and 2, members of the poly(ADP-ribose) polymerase family, have previously been shown to play a role in insulin-mediated glucose uptake in adipocytes. However, their precise mechanism of action, and their role in insulin action in other cell types, such as myocytes, remains elusive. Treatment of differentiated L6 myotubes with the small molecule tankyrase inhibitor XAV939 resulted in insulin resistance as determined by impaired insulin-stimulated glucose uptake. Proteomic analysis of XAV939-treated myotubes identified down-regulation of several glucose transporter GLUT4 storage vesicle (GSV) proteins including RAB10, VAMP8, SORT1 and GLUT4...
April 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29668892/sumoylation-of-xrcc1-activated-by-poly-adp-ribosyl-ation-regulates-dna-repair
#9
Ling-Yueh Hu, Che-Chang Chang, Yen-Sung Huang, Wen-Cheng Chou, Ying-Mei Lin, Chun-Chen Ho, Wei-Ting Chen, Hsiu-Ming Shih, Chia-Ni Hsiung, Pei-Ei Wu, Chen-Yang Shen
XRCC1 is an essential scaffold protein for base excision repair (BER) and helps to maintain genomic stability. XRCC1 has been indicated as a substrate for small ubiquitin-like modifier modification (SUMOylation); however, how XRCC1 SUMOylation is regulated in cells and how SUMOylated XRCC1 regulates BER activity are not well understood. Here we show that SUMOylation of XRCC1 is regulated in cells under methyl-methanesulfonate (MMS) treatment and facilitates BER. Poly(ADP-ribose) polymerase 1 (PARP1) is activated by MMS immediately and synthesizes poly(ADP-ribose) (PAR), which in turn promotes recruitment of SUMO E3 TOPORS to XRCC1 and facilitates XRCC1 SUMOylation...
April 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29668451/a-review-on-dna-repair-inhibition-by-parp-inhibitors-in-cancer-therapy
#10
REVIEW
Ashish P Shah, Chhagan N Patel, Dipen K Sureja, Kirtan P Sanghavi
The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells...
March 1, 2018: Folia Medica
https://www.readbyqxmd.com/read/29665822/toxoplasma-gondii-dense-granule-protein-15-induces-apoptosis-in-choriocarcinoma-jeg-3-cells-through-endoplasmic-reticulum-stress
#11
Wei Wei, Fangfang Zhang, He Chen, Yuanyuan Tang, Tian Xing, Qingli Luo, Li Yu, Jian Du, Jilong Shen, Linjie Zhang
BACKGROUND: Toxoplasma gondii, a single-celled parasite commonly found in mammals, has been shown to induce trophoblast cell apoptosis and subsequently cause fetal damage and abortion. Although dense granule protein 15 (GRA15) has been identified as a key component in innate immunity to T. gondii infection and its pathogenesis, its role in host cell apoptosis remains unclarified. METHODS: Type II GRA15 (GRA15II ) cDNA was inserted into a plasmid encoding enhanced green fluorescent protein (pEGFP)...
April 17, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29664094/analysis-of-poly-adp-ribose-polymerase-1-by-enzyme-initiated-auto-parylation-controlled-aggregation-of-hemin-graphene-nanocomposites
#12
Yong Liu, Xiaolin Xu, Haitang Yang, Ensheng Xu, Shuangshuang Wu, Wei Wei, Jin Chen
Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to damaged DNA and plays a key role in DNA repair, recombination, proliferation, and genomic stability. However, due to the poor electrochemical and optical activity of PARP-1 and its product PAR, only a few studies on its activity detection method have been reported. Herein, we report a simple and sensitive colorimetric strategy to monitor PARP-1 activity based on enzyme-initiated auto-PARylation-controlled aggregation of hemin-graphene nanocomposites (H-GNs)...
April 17, 2018: Analyst
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#13
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663662/glabridin-induces-apoptosis-and-cell-cycle-arrest-in-oral-cancer-cells-through-the-jnk1-2-signaling-pathway
#14
Chang-Tai Chen, Yi-Tzu Chen, Yi-Hsien Hsieh, Chia-Jui Weng, Jung-Chun Yeh, Shun-Fa Yang, Chiao-Wen Lin, Jia-Sin Yang
Glabridin, a flavonoid extracted from licorice (Glycyrrhiza glabra), possesses various biological properties, including anticancer activities. However, the effect of glabridin on oral cancer cell apoptosis and the underlying molecular mechanisms has not been elucidated. In this study, we demonstrated that glabridin treatment significantly inhibits cell proliferation in human oral cancer SCC-9 and SAS cell lines. Flow cytometric assays demonstrated that glabridin induced several features of apoptosis, such as sub-G1 phase cell increase and phosphatidylserine externalization...
April 16, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29661921/parp1-promotes-the-human-heat-shock-response-by-facilitating-hsf1-binding-to-dna
#15
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/29660759/parp-inhibitors-in-breast-cancer-bringing-synthetic-lethality-to-the-bedside
#16
REVIEW
Anita A Turk, Kari B Wisinski
Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29658592/in-vitro-cytotoxic-effect-of-parp-inhibitor-alone-and-in-combination-with-nab%C3%A2-paclitaxel-on-triple%C3%A2-negative-and-luminal-a-breast-cancer-cells
#17
Mehmet Topçul, İdi L Çeti N, Suna Özbaş Turan, Melek Özlem Kolusayin Ozar
In the present study, the in vitro cytotoxic effect of poly(ADP‑ribose) polymerase (PARP) inhibitor alone and in combination with nab‑paclitaxel was evaluated on human triple‑negative breast cancer (TNBC) cell line MDA‑MB‑231 and human luminal A breast cancer cell line MCF‑7. For this purpose, cell index (CI) values obtained from xCELLigence Real‑Time Cell Analysis (RTCA) DP instrument, mitotic index (MI), labelling index (LI) and apoptotic index (AI) analysis among cell kinetic parameters were used...
April 12, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29655793/inhibition-of-nlrp9b-attenuates-acute-lung-injury-through-suppressing-inflammation-apoptosis-and-oxidative-stress-in-murine-and-cell-models
#18
Qiu Yanling, Cheng Xiaoning, Bai Fei, Fang Liyun, Hu Huizhong, Sun Daqing
Acute lung injury (ALI), known a severe disease along with high morbidity and mortality, is lacking of specific therapies. Inflammation, apoptosis and oxidative stress are critical pathologies that contribute to ALI. Recently, there is study indicated that NLRP9b, a NOD-like receptor (NLR) member, is critical in modulation of inflammatory response. However, the effects of NLRP9b on sepsis-associated ALI, and the underlying molecular mechanism have not been understood. In the present study, the wild type (WT) and NLRP9b-knockout (NLRP9b-/- ) mice with C57B/L6 background were subjected to a cecal ligation and puncture (CLP) for ALI murine model establishment...
April 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29655723/thermal-behavior-of-inosine-5-monophosphate-in-acidic-form-and-as-alkali-and-alkaline-earth-salts
#19
J H F de Jesus, A P G Ferreira, E T G Cavalheiro
Inosine 5'-monophosphate in acidic form and its lithium, potassium, magnesium, calcium, strontium and barium were prepared from the sodium salt, characterized by elemental analysis and Fourier transform infrared spectroscopy and submitted to thermogravimetry (TG), differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermogravimetry coupled to infrared spectroscopy (TG-FTIR) of the volatile products evolved during heating. All the salts were hydrated containing from 4 to 7.5 H2 O...
August 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29653181/zh-1-enhances-the-anticancer-activity-of-gemcitabine-via-deoxyribonucleotide-synthesis-and-apoptotic-pathway-against-a549-cells
#20
Jianru Guo, Yan Li, Christopher Wai Kei Lam, Caiyun Wang, Meicun Yao, Wei Zhang
The purpose of this study was to investigate the inhibitory effect of ZH-1 ((6S,9aS,6aR,9bR)-6-(phenylcarbonyl)-6,6a,9a,9b-tetrahydro-8H-azolidino[3,4-a]b enzo [e]indolizine-7,9-dione) and its potential interactions with gemcitabine in A549 cells. MTT assay showed that the combined use of gemcitabine and ZH-1 presented a significant inhibition effect on A549 cell growth with the cell viability from 82.3 ± 5.6% to 51.0 ± 6.6%. The CI value was 0.60 suggesting a synergistic effect between these two drugs...
April 10, 2018: Food and Chemical Toxicology
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