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PARP-1

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https://www.readbyqxmd.com/read/28107648/parp-1-controls-the-adipogenic-transcriptional-program-by-parylating-c-ebp%C3%AE-and-modulating-its-transcriptional-activity
#1
Xin Luo, Keun Woo Ryu, Dae-Seok Kim, Tulip Nandu, Carlos J Medina, Rebecca Gupte, Bryan A Gibson, Raymond E Soccio, Yonghao Yu, Rana K Gupta, W Lee Kraus
Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPβ's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107013/quaternary-n-2-pyridyl-dabco-salts-one-pot-in-situ-formation-from-pyridine-n-oxides-and-reactions-with-nucleophiles-a-mild-and-selective-route-to-substituted-n-2-pyridyl-n-ethylpiperazines
#2
Dmitry I Bugaenko, Marina A Yurovskaya, Alexander V Karchava
The N-(2-pyridyl)-N'-ethylpiperazines are important structural motifs in several medicinally relevant compounds. Known synthetic methods toward these structures are multistep and generally based on the SNAr-chemistry; their applicability is significantly limited to substrates containing electron-withdrawing groups. Here we describe a new methodology for a rapid and modular access to this privileged scaffold. Importantly, the developed protocol proved to be very general and efficient for the substrates containing substituents of different electronic nature...
January 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28106777/neuroprotection-by-caffeine-in-hyperoxia-induced-neonatal-brain-injury
#3
Stefanie Endesfelder, Ulrike Weichelt, Evelyn Strauß, Anja Schlör, Marco Sifringer, Till Scheuer, Christoph Bührer, Thomas Schmitz
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28101214/parp-1-may-be-involved-in-angiogenesis-in-epithelial-ovarian-cancer
#4
Wei Wei, Yan Li, Shuqing Lv, Cancan Zhang, Yongjie Tian
Poly (ADP-ribose) polymerase 1 (PARP-1) is involved in DNA repair and has been implicated in chemoresistance. The present study investigated whether PARP-1 promotes angiogenesis in ovarian cancer. PARP-1 and vascular endothelial growth factor A (VEGF-A) expression and CD34(+) microvascular density (MVD) were assessed using immunohistochemistry in 60 human epithelial ovarian cancer specimens. PARP-1 was stably knocked-down in SKOV3 cells using a specific small interfering RNA (siRNA); angiogenic capacity was assessed using the human umbilical vein endothelial cell (HUVEC) tubule formation assay; and PARP-1 and VEGF-A expression were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099440/engagement-of-components-of-dna-break-repair-complex-and-nf%C3%AE%C2%BAb-in-hsp70a1a-transcription-upregulation-by-heat-shock
#5
Joyita Hazra, Pooja Mukherjee, Asif Ali, Soumita Poddar, Mahadeb Pal
An involvement of components of DNA-break repair (DBR) complex including DNA-dependent protein kinase (DNA-PK) and poly-ADP-ribose polymerase 1 (PARP-1) in transcription regulation in response to distinct cellular signalling has been revealed by different laboratories. Here, we explored the involvement of DNA-PK and PARP-1 in the heat shock induced transcription of Hsp70A1A. We find that inhibition of both the catalytic subunit of DNA-PK (DNA-PKc), and Ku70, a regulatory subunit of DNA-PK holo-enzyme compromises transcription of Hsp70A1A under heat shock treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28095779/poly-adp-ribose-polymerase-inhibitors-activate-the-p53-signaling-pathway-in-neural-stem-progenitor-cells
#6
Akiko Okuda, Suguru Kurokawa, Masanori Takehashi, Aika Maeda, Katsuya Fukuda, Yukari Kubo, Hyuma Nogusa, Tomoka Takatani-Nakase, Shujiro Okuda, Kunihiro Ueda, Seigo Tanaka
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1), which catalyzes poly(ADP-ribosyl)ation of proteins by using NAD(+) as a substrate, plays a key role in several nuclear events, including DNA repair, replication, and transcription. Recently, PARP-1 was reported to participate in the somatic cell reprogramming process. Previously, we revealed a role for PARP-1 in the induction of neural apoptosis in a cellular model of cerebral ischemia and suggested the possible use of PARP inhibitors as a new therapeutic intervention...
January 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28095625/potentiation-of-biological-effects-of-mesenchymal-stem-cells-in-ischemic-conditions-by-melatonin-via-upregulation-of-cellular-prion-protein-expression
#7
Jun Hee Lee, Yong-Seok Han, Sang Hun Lee
Mesenchymal stem cells (MSCs) are promising candidates for stem cell-based therapy in ischemic diseases. However, ischemic injury induces pathophysiological conditions, such as oxidative stress and inflammation, which diminish therapeutic efficacy of MSC-based therapy by reducing survival and functionality of transplanted MSCs. To overcome this problem, we explored the effects of melatonin on the proliferation, resistance to oxidative stress, and immunomodulatory properties of MSCs. Treatment with melatonin enhanced MSC proliferation and self-renewal via upregulation of cellular prion protein (PrP(C) ) expression...
January 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28079261/effect-of-parthanatos-on-ropivacaine-induced-damage-in-sh-sy5y-cells
#8
Ting Zheng, Chun-Ying Zheng, Xiao-Chun Zheng, Ruo-Guang Zhao, Yan-Qing Chen
Ropivacaine is one of the most common but toxic local anesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and NAD(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and Western blots were used to analyze the expression levels of PARP-1 and AIF after ropivacaine treatments with different concentrations and durations...
January 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28055012/aif-independent-parthanatos-in-the-pathogenesis-of-dry-age-related-macular-degeneration
#9
Ki-Hong Jang, Yun-Ju Do, Dongwon Son, Eunji Son, Jun-Sub Choi, Eunhee Kim
Cell death of retinal pigment epithelium (RPE) is characterized as an essential late-stage phenomenon of dry age-related macular degeneration (AMD). The aim of this study was to elucidate the molecular mechanism underlying RPE cell death after exposure to oxidative stress, which occurs often because of the anatomical location of RPE cells. ARPE-19, an established RPE cell line, exhibited necrotic features involving poly (ADP-ribose) polymerase-1 (PARP-1) activation in response to hydrogen peroxide (H2O2). ARPE-19 cells were resistant to H2O2 when PARP-1 was depleted using siRNA or inhibited by a pharmacological inhibitor of PARP-1, olaparib...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28053599/anticancer-properties-of-ester-derivatives-of-betulin-in-human-metastatic-melanoma-cells-me-45
#10
Małgorzata Drąg-Zalesińska, Marcin Drąg, Marcin Poręba, Sylwia Borska, Julita Kulbacka, Jolanta Saczko
BACKGROUND: Betulinic acid and betulin are triterpenes that have anticancer properties in various types of cancer. Unfortunately, the bioavailability and the bio-distribution of betulinic acid and its metabolic precursor, betulin are very low because of poor solubility in aqueous buffers. METHODS: In this study, we examined the anticancer properties of the ester derivatives of betulin compared to their precursors in a malignant melanoma cell line. We assessed five amino acid esters of betulin...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28052347/apoptotic-effects-of-bovine-apo-lactoferrin-on-hela-tumor-cells
#11
Carla Luzi, Fabrizia Brisdelli, Roberto Iorio, Argante Bozzi, Veronica Carnicelli, Antonio Di Giulio, Anna Rita Lizzi
Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12...
January 3, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28013023/metabolic-roles-of-poly-adp-ribose-polymerases
#12
REVIEW
András Vida, Judit Márton, Edit Mikó, Péter Bai
Poly(ADP-ribosyl)ation (PARylation) is an evolutionarily conserved reaction that had been associated with numerous cellular processes such as DNA repair, protein turnover, inflammatory regulation, aging or metabolic regulation. The metabolic regulatory tasks of poly(ADP-ribose) polymerases (PARPs) are complex, it is based on the regulation of metabolic transcription factors (e.g. SIRT1, nuclear receptors, SREBPs) and certain cellular energy sensors. PARP over-activation can cause damage to mitochondrial terminal oxidation, while the inhibition of PARP-1 or PARP-2 can induce mitochondrial oxidation by enhancing the mitotropic tone of gene transcription and signal transduction...
December 21, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28011424/green-synthesis-and-anticancer-potential-of-chalcone-linked-1-2-3-triazoles
#13
Pinki Yadav, Kashmiri Lal, Ashwani Kumar, Santosh Kumar Guru, Sundeep Jaglan, Shashi Bhushan
A series of chalcone linked-1,2,3-triazoles was synthesized via cellulose supported copper nanoparticle catalyzed click reaction in water. The structures of all the compounds were analyzed by IR, NMR and Mass spectral techniques. All the synthesized products were subjected to 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay against a panel of four human cancer cell lines (MCF-7, MIA-Pa-Ca-2, A549, HepG2) to check their anticancer potential. Compound 6h was found to be most active against all the tested cancer cell lines with IC50 values in the range of 4-11 μM and showed better or comparable activity to the reference drug against all the tested cell lines...
November 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28007593/down-regulation-of-msrb3-induces-cancer-cell-apoptosis-through-reactive-oxygen-species-production-and-intrinsic-mitochondrial-pathway-activation
#14
Geun-Hee Kwak, Tae-Hyoung Kim, Hwa-Young Kim
Methionine sulfoxide reductase B3 (MsrB3) is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues and has an antioxidant function. We have previously shown that depletion of MsrB3 suppresses the proliferation of normal mammalian cells by arresting cell cycle. In this study, we report the crucial role of MsrB3 in cancer cell death. Deficiency of MsrB3 induced cancer cell death, while MsrB3 overexpression stimulated cancer cell proliferation. MsrB3 depletion resulted in apoptotic cancer cell death through the activation of the intrinsic mitochondrial pathway...
December 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27999072/the-extracellular-isoform-of-superoxide-dismutase-has-a-significant-impact-on-cardiovascular-ischaemia-and-reperfusion-injury-during-cardiopulmonary-bypass
#15
Antonio Pinto, Moritz Benjamin Immohr, Annika Jahn, Alexander Jenke, Udo Boeken, Artur Lichtenberg, Payam Akhyari
OBJECTIVES: Cardiac surgery with cardiopulmonary bypass (CPB) provokes ischaemia and reperfusion injury (IRI). Superoxide is a main mediator of IRI and is detoxified by superoxide dismutases (SODs). Extracellular SOD (SOD3) is the prevailing isoform in the cardiovascular system. Its mutation is associated with elevated risk for ischaemic heart disease as epidemiological and experimental studies suggest. We investigated the influence of SOD3 on IRI in the context of CPB and hypothesized a protective role for this enzyme...
December 2016: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/27994507/catalpol-protects-pre-myelinating-oligodendrocytes-against-ischemia-induced-oxidative-injury-through-erk1-2-signaling-pathway
#16
Qiyan Cai, Teng Ma, Chengren Li, Yanping Tian, Hongli Li
The vulnerability of pre-myelinating oligodendrocytes (PreOLs) to ischemic injury plays an important role in the pathogenesis and progression of perinatal white matter injury. Although oxidative stress is thought to be a major pathogenic mechanism predisposing the PreOLs to injury, no effective therapies have been identified to date. The present study aimed to investigate the direct protective effects of catalpol, a potent antioxidant and free radical scavenger, on ischemia-induced oxidative damage in PreOLs and to explore whether the ERK1/2 signaling pathway contributed to the protection provided by catalpol...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27992945/inhibition-of-poly-adp-ribose-polymerase-may-have-preventive-potential-for-varicocoele-associated-testicular-damage-in-rats
#17
C Celik-Ozenci, N Kuscu, N E Gungor-Ordueri, A Tasatargil, P Sahin, H Durmus
Varicocele is ordinarily accompanied by testicular damage and male infertility. Several theories have been proposed to explain the detrimental effect of varicocele on testis tissue, including the possible effects of oxidative stress. The poly(ADP-ribose) polymerase (PARP) pathway has been established as a major downstream intracellular pathway of oxidative stress. Recently we have reported that PARP pathway has been activated in varicocele-induced rat testicular damage model. The aim of the present study was to investigate the possible protective effect of PARP inhibition in varicocele-associated testicular damage...
December 19, 2016: Andrology
https://www.readbyqxmd.com/read/27990620/role-of-peroxynitrite-induced-activation-of-poly-adp-ribose-polymerase-parp-in-circulatory-shock-and-related-pathological-conditions
#18
REVIEW
Badar Ul Islam, Safia Habib, Syed Amaan Ali, Moinuddin, Asif Ali
Peroxynitrite is a powerful oxidant, formed from the reaction of nitric oxide and superoxide. It is known to interact and modify different biological molecules such as DNA, lipids and proteins leading to alterations in their structure and functions. These events elicit various cellular responses, including cell signaling, causing oxidative damage and committing cells to apoptosis or necrosis. This review discusses nitrosative stress-induced modification in the DNA molecule that results in the formation of 8-nitroguanine and 8-oxoguanine, and its role in disease conditions...
December 19, 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27956242/fusaric-acid-induces-oxidative-stress-and-apoptosis-in-human-cancerous-oesophageal-sno-cells
#19
Nikita Devnarain, Charlette Tiloke, Savania Nagiah, Anil A Chuturgoon
Oesophageal cancer (OC) is a global problem incrementally incident among black South African males. The high incidence of OC may be due to the consumption of corn as a staple, often contaminated with mycotoxins. Fusaric acid (FA), a neglected mycotoxin, is known to disrupt mitochondrial energy metabolism, chelates divalent metal cations and induces cell death in plants. This study investigated FA-induced cytotoxicity and apoptotic induction in the SNO OC cell line. Cells were treated with FA (IC50 = 78.81 μg/mL; 24 h; MTT assay) and assayed for oxidative stress and membrane damage (TBARS, LDH cytotoxicity and glutathione), apoptotic induction (ATP levels, caspase-8, -9, -3/7 activities) (Luminometry), single strand DNA and nuclear fragmentation (Comet and Hoechst assay)...
December 9, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27936037/the-antioxidative-fraction-of-white-mulberry-induces-apoptosis-through-regulation-of-p53-and-nf%C3%AE%C2%BAb-in-eac-cells
#20
Ahm Khurshid Alam, Asm Sakhawat Hossain, Muhammad Ali Khan, Syed Rashel Kabir, Md Abu Reza, Md Mahbubur Rahman, Mohammad Saiful Islam, Md Aziz Abdur Rahman, Mamunur Rashid, Md Golam Sadik
In this study, the antioxidative fraction of white mulberry (Morus alba) was found to have an apotogenic effect on Ehrlich's ascites carcinoma cell-induced mice (EAC mice) that correlate with upregulated p53 and downregulated NFκB signaling. The antioxidant activities and polyphenolic contents of various mulberry fractions were evaluated by spectrophotometry and the ethyl acetate fraction (EAF) was selected for further analysis. Strikingly, the EAF caused 70.20% tumor growth inhibition with S-phase cell cycle arrest, normalized blood parameters including red/white blood cell counts and suppressed the tumor weight of EAC mice compared with untreated controls...
2016: PloS One
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