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https://www.readbyqxmd.com/read/28650468/mkp-1-suppresses-parp-1-degradation-to-mediate-cisplatin-resistance
#1
J Wang, D H Kho, J-Y Zhou, R J Davis, G S Wu
Understanding the mechanisms of platinum compound resistance, including cisplatin resistance, has important implications for improving cancer treatments. Previous studies identified a potential role for mitogen-activated protein kinase phosphatase-1 (MKP-1) in cisplatin resistance. This work focuses on the regulation of poly(ADP-ribose) polymerase-1 (PARP-1) expression by MKP-1. We found that MKP-1 overexpression stimulates PARP-1 and poly(ADP-ribose) (PAR) protein expression and cisplatin resistance while its downregulation suppresses PARP-1 and PAR protein expression and cisplatin resistance...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649682/rhodium-catalyzed-redox-neutral-coupling-of-phenidones-with-alkynes
#2
Zhoulong Fan, Heng Lu, Wei Li, Kaijun Geng, Ao Zhang
A switchable synthesis of N-substituted indole derivatives from phenidones via rhodium-catalyzed redox-neutral C-H activation has been achieved. In this protocol, we firstly disclosed that the reactivity of Rh(iii) catalysis could be enhanced through employing palladium acetate as an additive. Some representative features include external oxidant-free, applicable to terminal alkynes, short reaction time and operational simplicity. The utility of this method is further showcased by the economical synthesis of potent anticancer PARP-1 inhibitors...
June 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#3
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622906/discovery-of-novel-quinazoline-2-4-1h-3h-dione-derivatives-as-potent-parp-2-selective-inhibitors
#4
Hailong Zhao, Ming Ji, Guonan Cui, Jie Zhou, Fangfang Lai, Xiaoguang Chen, Bailing Xu
The PARP-2 selective inhibitor is important for clarifying specific roles of PARP-2 in the pathophysiological process and developing desired drugs with reduced off-target side effects. In this work, a series of novel quinazoline-2,4(1H,3H)-dione derivatives was designed and synthesized to explore isoform selective PARP inhibitors. As a result, compound 11a (PARP-1 IC50=467nM, PARP-2 IC50=11.5nM, selectivity PARP-1/PARP-2=40.6) was disclosed as the most selective PARP-2 inhibitor with high potency to date. The binding features of compound 11a within PARP-1 and PARP-2 were investigated respectively to provide useful insights for the further construction of new isoform selective inhibitors of PARP-1 and PARP-2 by using CDOCKER program...
May 26, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28620309/inhibition-of-the-trpm2-and-trpv1-channels-through-hypericum-perforatum-in-sciatic-nerve-injury-induced-rats-demonstrates-their-key-role-in-apoptosis-and-mitochondrial-oxidative-stress-of-sciatic-nerve-and-dorsal-root-ganglion
#5
Fuat Uslusoy, Mustafa Nazıroğlu, Bilal Çiğ
Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28616020/minocycline-targets-multiple-secondary-injury-mechanisms-in-traumatic-spinal-cord-injury
#6
REVIEW
Robert B Shultz, Yinghui Zhong
Minocycline hydrochloride (MH), a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615517/mtor-signaling-mediates-resistance-to-tankyrase-inhibitors-in-wnt-driven-colorectal-cancer
#7
Tetsuo Mashima, Yoko Taneda, Myung-Kyu Jang, Anna Mizutani, Yukiko Muramatsu, Haruka Yoshida, Ayana Sato, Noritaka Tanaka, Yoshikazu Sugimoto, Hiroyuki Seimiya
Activation of Wnt/β-catenin signaling is essential for colorectal carcinogenesis. Tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, is a positive regulator of the Wnt/β-catenin signaling. Accordingly, tankyrase inhibitors are under preclinical development for colorectal cancer (CRC) therapy. However, Wnt-driven colorectal cancer cells are not equally sensitive to tankyrase inhibitors, and cellular factors that affect tankyrase inhibitor sensitivity remain elusive. Here, we established a tankyrase inhibitor-resistant cell line, 320-IWR, from Wnt/β-catenin-dependent CRC COLO-320DM cells...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614779/the-effect-of-the-nitroxide-pirolin-on-oxidative-stress-induced-by-doxorubicin-and-taxanes-in-the-rat-brain
#8
S Tabaczar, J Czepas, A Koceva-Chyla, E Kilanczyk, J Piasecka-Zelga, K Gwozdzinski
The anticancer drugs doxorubicin (DOX), paclitaxel (PTX) and docetaxel (DTX) have been proven to induce oxidative stress (OS)-dependent side-effects in non-targeted tissues. In normal conditions, the blood-brain barrier (BBB) prevents these drugs from penetrating into the brain. However, some studies have demonstrated that small amounts of DOX can penetrate the brain via an oxidatively impaired BBB and cause damage, which suggests that including antioxidants in chemotherapy could possibly protect the brain against the toxicity of anticancer drugs...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28608237/exogenous-adipokine-peptide-resistin-protects-against-focal-cerebral-ischemia-reperfusion-injury-in-mice
#9
Jiangtao Zhu, Di Wu, Chenyu Zhao, Man Luo, Ronald C Hamdy, Balvin H L Chua, Xingshun Xu, Zhigang Miao
Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28608226/blocking-rhoa-rock-inhibits-the-pathogenesis-of-pemphigus-vulgaris-by-suppressing-oxidative-stress-and-apoptosis-through-tak1-nod2-mediated-nf-%C3%AE%C2%BAb-pathway
#10
Junqin Liang, Xuewen Zeng, Yilinuer Halifu, Wenjing Chen, Fengxia Hu, Peng Wang, Huan Zhang, Xiaojing Kang
Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein...
June 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28608001/anti-zn-2-toxicity-of-4-hydroxybenzyl-alcohol-in-astrocytes-and-neurons-contribute-to-a-robust-neuroprotective-effects-in-the-postischemic-brain
#11
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn(2+) toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects...
June 12, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28599464/dna-repair-genes-polymorphisms-and-genetic-susceptibility-to-philadelphia-negative-myeloproliferative-neoplasms-in-a-portuguese-population-the-role-of-base-excision-repair-genes-polymorphisms
#12
Ana P Azevedo, Susana N Silva, João P De Lima, Alice Reichert, Fernando Lima, Esmeraldina Júnior, José Rueff
The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598299/proper-sister-chromatid-disjunction-requires-cda-and-parp-1
#13
Jean-Sébastien Hoffmann, Pierre Cordelier
No abstract text is available yet for this article.
June 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28598106/-the-protective-effect-of-inhibition-of-parp-1-on-inflammation-induced-by-pm2-5-in-human-bronchial
#14
Qing Huang, Jing-Jing Zhang, Zun-Zhen Zhang
OBJECTIVES: To explore whether the inhibition of poly ADP-ribose polymerase-1(PARP-1) could attenuated inflammation induced by fine particulate matter (PM2.5) in human bronchial epithelial cell line. METHODS: Cell viability was detected by Trypan Blue assay after incubated with PM2.5 for 24 h.PM2.5 doses no more than 600 μg/mL were utilized in the following experiments.In order to observe how PARP-1 would effect the expression of nuclear factor-κB p65 and inducible nitric oxide synthase (iNOS),cells were respectively treated with 600 μg/mL PM2...
November 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28593135/evaluation-of-cell-death-pathways-initiated-by-antitumor-drugs-melatonin-and-valproic-acid-in-bladder-cancer-cells
#15
Siwei Liu, Bilin Liang, Huiting Jia, Yuhan Jiao, Zhongqiu Pang, Yongye Huang
Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid (VPA) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up-regulation of certain genes related to apoptosis (TNFRSF10A and TNFRSF10B), autophagy (BECN, ATG3 and ATG5) and necrosis (MLKL, PARP-1 and RIPK1)...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28586007/apg-1252-12a-induces-mitochondria-dependent-apoptosis-through-inhibiting-the-antiapoptotic-proteins-bcl-2-bcl-xl-in-hl-60-cells
#16
Jing Wang, Dajun Yang, Qiuyun Luo, Miaozhen Qiu, Lin Zhang, Baoxia Li, Haibo Chen, Hanjie Yi, Xianglei Yan, Shuxia Li, Jian Sun
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers...
June 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28579325/a-peptide-disrupting-the-d2r-dat-interaction-protects-against-dopamine-neurotoxicity
#17
Ping Su, Fang Liu
Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels...
June 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28576564/cognitive-deficits-induced-by-combined-exposure-of-stress-and-alcohol-mediated-through-oxidative-stress-parp-pathway-in-the-hippocampus
#18
Rajat Pant, Ashok Jangra, Mohit Kwatra, Tavleen Singh, Pawan Kushwah, Babul Kumar Bezbaruah, Satendra Singh Gurjar, Swopna Phukan
Several studies reported that stress can enhance the consumption of alcohol in humans and animals. However, the combinatorial effect of stress and alcohol on cognitive function and neurochemical alterations is quite understudied. In the present study, we have elucidated the involvement of oxidative stress-PARP cascade in alcohol and restraint stress (RS)-exposed animals using a PARP inhibitor, 1,5-isoquinolinediol (3mg/kg for 14days). Male Swiss albino mice were given alcohol (ALC) or RS (2h per day) or both in ALC+RS group for 28days...
May 30, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28560323/ctcf-facilitates-dna-double-strand-break-repair-by-enhancing-homologous-recombination-repair
#19
Khalid Hilmi, Maïka Jangal, Maud Marques, Tiejun Zhao, Amine Saad, Chenxi Zhang, Vincent M Luo, Alasdair Syme, Carlis Rejon, Zhenbao Yu, Asiev Krum, Marc R Fabian, Stéphane Richard, Moulay Alaoui-Jamali, Alexander Orthwein, Luke McCaffrey, Michael Witcher
The repair of DNA double-strand breaks (DSBs) is mediated via two major pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR) repair. DSB repair is vital for cell survival, genome stability, and tumor suppression. In contrast to NHEJ, HR relies on extensive homology and templated DNA synthesis to restore the sequence surrounding the break site. We report a new role for the multifunctional protein CCCTC-binding factor (CTCF) in facilitating HR-mediated DSB repair. CTCF is recruited to DSB through its zinc finger domain independently of poly(ADP-ribose) polymers, known as PARylation, catalyzed by poly(ADP-ribose) polymerase 1 (PARP-1)...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28556445/induction-of-necroptosis-in-cancer-stem-cells-by-a-nickel-ii-dithiocarbamate-phenanthroline-complex
#20
Marie Flamme, Paul Cressey, Chunxin Lu, Peter Bruno, Arvin Eskandari, Michael Hemann, Graeme Hogarth, Kogularamanan Suntharalingam
The cytotoxic properties of a series of nickel(II)-dithiocarbamate phenanthroline complexes is reported. The complexes, 1-6 kill bulk cancer cells and cancer stem cells (CSCs) with micromolar potency. Two of the complexes, 2 and 6 kill breast cancer stem cell (CSC)-enriched HMLER-shEcad cells 2-fold better than breast CSC-depleted HMLER cells. Complex 2 inhibits mammosphere formation to a better extent than salinomycin (a CSC-specific toxin). Detailed mechanistic studies suggest that 2 induces CSC death by necroptosis, a programmed form of necrosis...
May 26, 2017: Chemistry: a European Journal
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