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https://www.readbyqxmd.com/read/28819445/dna-dependent-protein-kinase-catalytic-subunit-functions-in-metastasis-and-influences-survival-in-advanced-stage-laryngeal-squamous-cell-carcinoma
#1
Sha-Sha He, Yong Chen, Xiao-Ming Shen, Hong-Zhi Wang, Peng Sun, Jun Dong, Gui-Fang Guo, Ju-Gao Chen, Liang-Ping Xia, Pei-Li Hu, Hui-Juan Qiu, Shou-Sheng Liu, Yi-Xin Zhou, Wei Wang, Wei-Han Hu, Xiu-Yu Cai
Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28802226/taraxerol-a-pentacyclic-triterpenoid-from-abroma-augusta-leaf-attenuates-diabetic-nephropathy-in-type-2-diabetic-rats
#2
Ritu Khanra, Niloy Bhattacharjee, Tarun K Dua, Ashis Nandy, Achintya Saha, Jatin Kalita, Prasenjit Manna, Saikat Dewanjee
Persistent hyperglycaemia coupled with inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). Present study examined the therapeutic potential of taraxerol isolated from the methanol extract of Abroma augusta leaf against DN using rodent model of type 2 diabetes (T2D). T2D was experimentally induced by high fat diet and a single low-single dose of streptozotocin (35mg/kg, i.p.). Accumulation of serum creatinine, urea, and uric acid, activation of lactate dehydrogenase and creatinin kinase, and release of urinary albumin represented the glomerular damage and the progression of nephropathy in T2D rats...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28780472/different-profiles-of-the-mrna-levels-of-dna-repair-genes-in-mcf-7-and-sh-sy5y-cells-after-treatment-with-combination-of-cisplatin-50-hz-electromagnetic-field-and-bleomycin
#3
Fatemeh Sanie-Jahromi, Mostafa Saadat
Neurotoxicity is known to be a major dose-limiting adverse effect of cisplatin (CDDP), alone or in combination with other chemicals. DNA repair capacity serve as a neuroprotective factor against CDDP. The purpose of this study was to evaluate the effect of 50-Hz electromagnetic field (EMF) in combination with CDDP and bleomycin (Bleo) on expression of some of DNA repair genes (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) in MCF-7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. MCF-7 and SH-SY5Y cells were pre-treated with CDDP in the presence or absence of EMF and then exposed to different concentration of Bleo...
August 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28771739/endostatin-sensitizes-p53-deficient-non-small-cell-lung-cancer-to-genotoxic-chemotherapy-by-targeting-dna-pkcs
#4
Lin Jia, Xin-An Lu, Guanghua Liu, Shan Wang, Min Xu, Yang Tian, Shaosen Zhang, Yan Fu, Yongzhang Luo
Endostatin was discovered as an endogenous angiogenesis inhibitor with broad-spectrum antitumor activities. Although clinical efficacy was observed when combining endostatin with standard chemotherapy for non-small cell lung cancer (NSCLC), as well as other cancer types, the specific mechanisms underlying the benefit of endostatin are not completely understood. Extensive investigations suggest that endostatin is a multifunctional protein possessing more than anti-angiogenic activity. Here, we identified that endostatin exerts a direct chemosensitizing effect on p53-deficient tumor cells...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28767037/cryo-em-structure-of-the-saga-and-nua4-coactivator-subunit-tra1-at-3-7-angstrom-resolution
#5
Luis Miguel Diaz-Santin, Natasha Lukoyanova, Emir Aciyan, Alan Cm Cheung
Coactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to 3.7 Å resolution, revealing an extensive network of alpha-helical solenoids organized into a diamond ring conformation and is strikingly reminiscent of DNA-PKcs, suggesting a direct role for Tra1 in DNA repair...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28762752/oxidative-stress-in-mesenchymal-stem-cell-senescence-regulation-by-coding-and-non-coding-rnas
#6
Rosa Vono, Eva Jover Garcia, Gaia Spinetti, Paolo Madeddu
SIGNIFICANCE: Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into mesodermal lineages, play an important role in tissue homeostasis and regeneration. In different organs, a subpopulation of MSCs is located near to the vasculature and possibly represents the original source of lineage-committed mesenchymal progenitors. Recent Advances. The plasticity and immune characteristics of MSCs render them a preferential tool for regenerative cell therapy. CRITICAL ISSUES: The culture expansion needed before MSC transplantation is associated with cellular senescence...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28761330/epigenetic-memory-of-oxidative-stress-does-nephrilin-exert-its-protective-effects-via-rac1
#7
Desmond D Mascarenhas, David N Herndon, Istvan Arany
AIM: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2), exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox) via PKCs, Prex1 and p66shc...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28759779/synthetic-lethality-between-murine-dna-repair-factors-xlf-and-dna-pkcs-is-rescued-by-inactivation-of-ku70
#8
Mengtan Xing, Magnar Bjørås, Jeremy A Daniel, Frederick W Alt, Valentyn Oksenych
DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3...
July 26, 2017: DNA Repair
https://www.readbyqxmd.com/read/28758831/tet1-deficiency-attenuates-the-dna-damage-response-and-promotes-resistance-to-dna-damaging-agents
#9
Jonathan B Coulter, Hernando Lopez-Bertoni, Katherine J Kuhns, Richard S Lee, John Laterra, Joseph P Bressler
Recent studies have shown that loss of TET1 may play a significant role in the formation of tumors. Because genomic instability is a hallmark of cancer, we examined the potential involvement of ten-eleven translocation 1 (TET1) in the DNA damage response (DDR). Here we demonstrate that, in response to clinically relevant doses of ionizing radiation (IR), human glial cells made TET1-deficient with lentiviral vectors displayed greater numbers of colony forming units and lower levels of apoptotic markers compared to glial cells transduced with control vectors; yet, they harbored greater DNA strand breaks...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28758638/influenza-virus-recruits-host-protein-kinase-c-to-control-assembly-and-activity-of-its-replication-machinery
#10
Arindam Mondal, Anthony R Dawson, Gregory K Potts, Elyse C Freiberger, Steven F Baker, Lindsey A Moser, Kristen A Bernard, Joshua J Coon, Andrew Mehle
Influenza virus expresses transcripts early in infection and transitions towards genome replication at later time points. This process requires de novo assembly of the viral replication machinery, large ribonucleoprotein complexes (RNPs) composed of the viral polymerase, genomic RNA and oligomeric nucleoprotein (NP). Despite the central role of RNPs during infection, the factors dictating where and when they assemble are poorly understood. Here we demonstrate that human protein kinase C (PKC) family members regulate RNP assembly...
July 31, 2017: ELife
https://www.readbyqxmd.com/read/28750002/dna-pkcs-controls-calcineurin-mediated-il-2-production-in-t-lymphocytes
#11
Ara Kim Wiese, Marie Schluterman Burdine, Richard H Turnage, Alan J Tackett, Lyle J Burdine
Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity in mammals results in severe combined immuno-deficiency (SCID). This SCID phenotype has been postulated to be due solely to the function of DNA-PKcs in V(D)J recombination, a process critical for lymphocyte maturation. However; we show that DNA-PKcs is required for IL-2 production via regulation of the calcineurin signaling pathway. Reducing DNA-PKcs activity in activated T cells either by shRNA or an inhibitor significantly reduced IL-2 production by blocking calcineurin activity and the translocation of NFAT into the nucleus...
2017: PloS One
https://www.readbyqxmd.com/read/28706768/dna-pk-and-p38-mapk-a-kinase-collusion-in-alzheimer-s-disease
#12
Jyotshna Kanungo
The pathogenesis of Alzheimer's disease (AD), characterized by prevalent neuronal death and extracellular deposit of amyloid plaques, is poorly understood. DNA lesions downstream of reduced DNA repair ability have been reported in AD brains. Neurons predominantly use a mechanism to repair double-strand DNA breaks (DSB), which is non-homologous end joining (NHEJ). NHEJ requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 and p70 subunits...
2017: Brain Disorders & Therapy
https://www.readbyqxmd.com/read/28702857/protein-kinase-c-and-cardiac-dysfunction-a-review
#13
REVIEW
Raphael M Singh, Emanuel Cummings, Constantinos Pantos, Jaipaul Singh
Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually...
July 12, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28700980/aurora-a-kinase-regulates-non-homologous-end-joining-and-poly-adp-ribose-polymerase-function-in-ovarian-carcinoma-cells
#14
Thuy-Vy Do, Jeff Hirst, Stephen Hyter, Katherine F Roby, Andrew K Godwin
Ovarian cancer is usually diagnosed at late stages when cancer has spread beyond the ovary and patients ultimately succumb to the development of drug-resistant disease. There is an urgent and unmet need to develop therapeutic strategies that effectively treat ovarian cancer and this requires a better understanding of signaling pathways important for ovarian cancer progression. Aurora A kinase (AURKA) plays an important role in ovarian cancer progression by mediating mitosis and chromosomal instability. In the current study, we investigated the role of AURKA in regulating the DNA damage response and DNA repair in ovarian carcinoma cells...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699908/expression-of-protein-kinase-c-gamma-promotes-cell-migration-in-colon-cancer
#15
Catríona M Dowling, Sheri L Hayes, James J Phelan, Mary Clare Cathcart, Stephen P Finn, Brian Mehigan, Paul McCormick, John C Coffey, Jacintha O'Sullivan, Patrick A Kiely
Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an intractable target in cancer therapies. Traditionally it was accepted that PKCs act as tumour promoters, however new research suggests that PKCs may play an important role in the suppression of cancer. A challenge in targeting PKCs is the limited data available in patient samples. One of the PKC isozymes, PKC gamma, is thought to be present only in the brain and has been largely neglected in the context of cancer. Analysis of gene expression levels of PKC gamma in patient matched normal and colon cancer tissue samples revealed an up-regulation of the gene in the cancer tissue of 54% of the patients examined...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698766/apple-flavonoids-suppress-carcinogen-induced-dna-damage-in-normal-human-bronchial-epithelial-cells
#16
Vazhappilly Cijo George, H P Vasantha Rupasinghe
SCOPE: Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4) against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. METHODS AND RESULTS: AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK), NNK acetate (NNK-Ae), methotrexate (MTX), and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28696258/effects-of-dna-end-configuration-on-xrcc4-dna-ligase-iv-and-its-stimulation-of-artemis-activity
#17
Christina A Gerodimos, Howard H Y Chang, Go Watanabe, Michael R Lieber
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4:DNA ligase IV (X4:LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5' and 3' overhangs...
July 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28676397/feedback-autophagy-activation-as-a-key-resistance-factor-of-ku-0060648-in-colorectal-cancer-cells
#18
Mintao Mao, Yumei Liu, Xinhai Gao
The current study evaluated the potential anti-colorectal cancer (CRC) activity by Ku-0060648, a novel DNA-PKcs and PI3K duel inhibitor. In both CRC cell lines (HCT-116 and HT-29) and primary human colon cancer cells, Ku-0060648 exposure at nM concentrations efficiently inhibited cell proliferation. Meanwhile, Ku-0060648 provoked apoptosis in CRC cells. Ku-0060648 was yet ineffective to the normal colon epithelial cells. Ku-0060648 blocked PI3K-AKT-mTOR cascade and in-activated DNA-PKcs in CRC cells. Intriguingly, Ku-0060648 treatment induced feedback autophagy activation in HCT-116 cells...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28673093/di-2-ethylhexyl-phthalate-suppresses-il-12p40-production-by-gm-csf-dependent-macrophages-via-the-ppar%C3%AE-tnfaip3-traf6-axis-after-lipopolysaccharide-stimulation
#19
R Yamaguchi, A Sakamoto, T Yamamoto, S Narahara, H Sugiuchi, A Hisada, T Katoh, Y Yamaguchi
Activation of peroxisome proliferator-activated receptor α (PPARα) by di-(2-ethylhexyl) phthalate (DEHP) has an anti-inflammatory effect. This study investigated the potential combined influence of PPARα, tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), and tumor necrosis factor receptor-associated factor 6 (TRAF6) on interleukin (IL)-12p40 production by macrophages exposed to DEHP and stimulated with lipopolysaccharide (LPS). LPS upregulated IL-12p40 expression by granulocyte-macrophage colony-stimulating factor-dependent macrophages (on day 9 of culture), whereas adding DEHP to cultures significantly attenuated the response of IL-12p40 to LPS stimulation...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28671468/synthesis-and-evaluation-of-dimeric-derivatives-of-diacylglycerol-lactones-as-protein-kinase-c-ligands
#20
Nami Ohashi, Ryosuke Kobayashi, Wataru Nomura, Takuya Kobayakawa, Agnes Czikora, Brienna K Herold, Nancy E Lewin, Peter M Blumberg, Hirokazu Tamamura
Protein kinase C (PKC) mediates a central cellular signal transduction pathway involved in disorders such as cancer and Alzheimer's disease. PKC is regulated by binding of the second messenger sn-1,2-diacylglycerol (DAG) to its tandem C1 domains, designated C1a and C1b, leading both to PKC activation and to its translocation to the plasma membrane and to internal organelles. Depending on the isoform, there may be differences in the ligand selectivity of the C1a and C1b domains, and there is different spacing between the C1 domains of the conventional and novel PKCs...
August 16, 2017: Bioconjugate Chemistry
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