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https://www.readbyqxmd.com/read/29227732/%C3%AE-8-oxoguanine-dna-glycosylase-overexpression-reduces-oxidative-stress-induced-mitochondrial-dysfunction-and-apoptosis-through-the-jnk-signaling-pathway-in-human-bronchial-epithelial-cells
#1
Ziying Lin, Wenya Xu, Chunyan Li, Yahong Wang, Lawei Yang, Bao'an Zou, Shenglan Gao, Weimin Yao, Zeqing Song, Gang Liu
8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that α-OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of β-OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed β-OGG1 has the same role as α-OGG1 in protecting human bronchial epithelial cells from apoptosis and mitochondrial dysfunction. Furthermore, flow cytometry, confocal microscopy, and western blotting showed that the overexpression of β-OGG1 could block oxidant-induced apoptosis in human bronchial epithelial cells...
December 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29209987/genetic-investigation-of-polymorphic-ogg1-and-mutyh-genes-towards-increased-susceptibility-in-lung-adenocarcinoma-and-its-impact-on-overall-survival-of-lung-cancer-patients-treated-with-platinum-based-chemotherapy
#2
Amrita Singh, Navneet Singh, Digambar Behera, Siddharth Sharma
Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway. OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer cases and 330 controls was followed by genotyping making use of PCR-RFLP. Logistic regression was done to analyze the risk towards lung cancer...
December 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29207315/8-oxoguanine-dna-glycosylase-ogg1-controls-hepatic-gluconeogenesis
#3
Katja Scheffler, Lyudmila Rachek, Panpan You, Alexander D Rowe, Wei Wang, Anna Kuśnierczyk, Lene Kittelsen, Magnar Bjørås, Lars Eide
Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the base excision repair pathway. Here, we tested the hypothesis that changes in liver metabolism as under fasting/feeding conditions would be sensed by liver mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild type (WT) and ogg1-/- mice were either fed ad libitum or subjected to fasting for 24h, and the corresponding effects on liver gene expression, DNA damage, as well as serum values were analyzed...
November 28, 2017: DNA Repair
https://www.readbyqxmd.com/read/29165690/the-regulatory-g4-motif-of-the-kirsten-ras-kras-gene-is-sensitive-to-guanine-oxidation-implications-on-transcription
#4
Susanna Cogoi, Annalisa Ferino, Giulia Miglietta, Erik B Pedersen, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145655/paternal-exposure-to-environmental-chemical-stress-affectsmale-offspring-s-hepatic-mitochondria
#5
Roger Godschalk, Alex Remels, Camiel Hoogendoorn, Jan van Benthem, Mirjam Luijten, Nur Duale, Gunnar Brunborg, Ann-Karin Olsen, Freek G Bouwman, Armelle Munnia, Marco Peluso, Edwin Mariman, Frederik Jan van Schooten
Pre-conceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29139108/a-3-untranslated-region-polymorphism-rs2304277-in-the-dna-repair-pathway-gene-ogg1-is-a-novel-risk-modulator-for-urothelial-bladder-carcinoma
#6
Tayyaba Ahmed, Saira Nawaz, Rabia Noreen, Kashif Sardar Bangash, Abdur Rauf, Muhammad Younis, Khursheed Anwar, Muhammad Athar Khawaja, Maleeha Azam, Abid Ali Qureshi, Saeed Akhter, Lambertus A Kiemeney, Raheel Qamar, Syeda Hafiza Benish Ali
Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)GG = 3...
November 15, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/29133960/divergent-roles-for-clusterin-in-lung-injury-and-repair
#7
David M Habiel, Ana Camelo, Milena Espindola, Timothy Burwell, Richard Hanna, Elena Miranda, Alan Carruthers, Matthew Bell, Ana Lucia Coelho, Hao Liu, Fernanda Pilataxi, Lori Clarke, Ethan Grant, Arthur Lewis, Bethany Moore, Darryl A Knight, Cory M Hogaboam, Lynne A Murray
Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike normal and COPD lungs, IPF lungs were characterized by significantly increased extracellular Clusterin whereas the inverse was evident for intracellular Clusterin. In vitro and in vivo studies demonstrated that extracellular Clusterin promoted epithelial cell apoptosis while intercellular Clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29129468/inhibition-of-rac1-ameliorates-neuronal-oxidative-stress-damage-via-reducing-bcl-2-rac1-complex-formation-in-mitochondria-through-pi3k-akt-mtor-pathway
#8
Yundan Pan, Na Wang, Pingping Xia, E Wang, Qulian Guo, Zhi Ye
Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria...
November 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-preserve-the-genome-and-improve-stroke-recovery
#9
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29123531/chronic-obstructive-pulmonary-disease-derived-circulating-cells-release-il-18-and-il-33-under-ultrafine-particulate-matter-exposure-in-a-caspase-1-8-independent-manner
#10
Gianluigi De Falco, Chiara Colarusso, Michela Terlizzi, Ada Popolo, Michela Pecoraro, Mario Commodo, Patrizia Minutolo, Mariano Sirignano, Andrea D'Anna, Rita P Aquino, Aldo Pinto, Antonio Molino, Rosalinda Sorrentino
Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108254/the-impacts-of-genetic-polymorphisms-in-genes-of-base-excision-repair-pathway-on-the-efficacy-and-acute-toxicities-of-chemo-radiotherapy-in-patients-with-nasopharyngeal-carcinoma
#11
Jing Wang, Chengxian Guo, Xiaochang Gong, Fan Ao, Yuling Huang, Lihua Huang, Yiqiang Tang, Chunling Jiang, Xiaoxue Xie, Qing Dong, Min Huang, Jingao Li
Purpose: To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). Methods: We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101721/restoration-of-cognitive-performance-in-mice-carrying-a-deficient-allele-of-8-oxoguanine-dna-glycosylase-by-x-ray-irradiation
#12
Tim Hofer, Nur Duale, Martine Muusse, Dag Marcus Eide, Hildegunn Dahl, Fernando Boix, Jannike M Andersen, Ann Karin Olsen, Oddvar Myhre
Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1)(+/-) (heterozygote) and Ogg1(+/+) (wild type, WT) mice, to study whether a single acute X-ray challenge (0...
November 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29100183/microcystin-lr-increases-genotoxicity-induced-by-aflatoxin-b1-through-oxidative-stress-and-dna-base-excision-repair-genes-in-human-hepatic-cell-lines
#13
Wenyi Liu, Lingqiao Wang, Chuanfen Zheng, Lebin Liu, Jia Wang, Daibo Li, Yao Tan, Xilong Zhao, Lixiong He, Weiqun Shu
Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) simultaneously exist in polluted food and water in humid and warm areas, and each has been reported to be genotoxic to liver and associated with hepatocellular carcinoma (HCC). However, the genotoxic effects of the two biotoxins in combination and potential mechanism remain unknown. We treated the human hepatic cell line HL7702 with AFB1 and MC-LR together at different ratios, examined their genotoxic effects using micronuclei and comet assays, and evaluated the possible mechanism by measuring oxidative stress markers and DNA base excision repair (BER) genes...
October 31, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29098062/mutation-spectrum-induced-by-8-bromoguanine-a-base-damaged-by-reactive-brominating-species-in-human-cells
#14
Kazuya Shinmura, Hisami Kato, Masanori Goto, Hong Tao, Yusuke Inoue, Satoki Nakamura, Haruki Yoshida, Emi Tsuzaki, Haruhiko Sugimura
To date, the types of mutations caused by 8-bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed a supF forward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29046123/differential-effects-of-silver-nanoparticles-on-dna-damage-and-dna-repair-gene-expression-in-ogg1-deficient-and-wild-type-mice
#15
Sameera Nallanthighal, Cadia Chan, Thomas M Murray, Aaron P Mosier, Nathaniel C Cady, Ramune Reliene
Due to extensive use in consumer goods, it is important to understand the genotoxicity of silver nanoparticles (AgNPs) and identify susceptible populations. 8-Oxoguanine DNA glycosylase 1 (OGG1) excises 8-oxo-7,8-dihydro-2-deoxyguanine (8-oxoG), a pro-mutagenic lesion induced by oxidative stress. To understand whether defects in OGG1 is a possible genetic factor increasing an individual's susceptibly to AgNPs, we determined DNA damage, genome rearrangements, and expression of DNA repair genes in Ogg1-deficient and wild type mice exposed orally to 4 mg/kg of citrate-coated AgNPs over a period of 7 d...
October 19, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29027485/concentration-dependent-effect-of-fumonisin-b1-on-apoptosis-in-oesophageal-cancer-cells
#16
R B Khan, A Phulukdaree, A A Chuturgoon
The geographical distribution of oesophageal cancer is linked to the exposure of fumonisin B1 (FB1), a mycotoxin produced by fungi that contaminates staple food worldwide. Non-genotoxic carcinogens like FB1 disturb homeostasis through increased cell proliferation or suppression of apoptosis. This study investigated the involvement of FB1 (0-20 μM) in spindle-shaped N-cadherin (+) CD45 (-) osteoblastic (SNO) cell death. Cell viability and death were assessed using the MTS and Annexin V-Fluos assays, respectively...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29027306/fenton-reaction-induced-renal-carcinogenesis-in-mutyh-deficient-mice-exhibits-less-chromosomal-aberrations-than-the-rat-model
#17
Guang Hua Li, Shinya Akatsuka, Shan Hwu Chew, Li Jiang, Takahiro Nishiyama, Akihiko Sakamoto, Takashi Takahashi, Mitsuru Futakuchi, Hiromu Suzuki, Kunihiko Sakumi, Yusaku Nakabeppu, Shinya Toyokuni
Oxidative stress including iron excess has been associated with carcinogenesis. The level of 8-oxoguanine, a major oxidatively modified base in DNA, is maintained very low by three distinct enzymes, encoded by OGG1, MUTYH and MTH1. Germline biallelic inactivation of MUTYH represents a familial cancer syndrome called MUTYH-associated polyposis. Here, we used Mutyh-deficient mice to evaluate renal carcinogenesis induced by ferric nitrilotriacetate (Fe-NTA). Although the C57BL/6 background is cancer-resistant, a repeated intraperitoneal administration of Fe-NTA induced a high incidence of renal cell carcinoma (RCC; 26...
October 13, 2017: Pathology International
https://www.readbyqxmd.com/read/28986302/activation-of-nrf2-might-reduce-oxidative-stress-in-human-granulosa-cells
#18
Nana Akino, Osamu Wada-Hiraike, Hiromi Terao, Harunori Honjoh, Wataru Isono, Houju Fu, Mana Hirano, Yuichiro Miyamoto, Michihiro Tanikawa, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Kaori Koga, Katsutoshi Oda, Kei Kawana, Tomoyuki Fujii, Yutaka Osuga
Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is one of the most important defense mechanisms against oxidative stress (OS). It is well documented that equilibration status of OS plays fundamental roles in human reproductive medicine, and the physiological role of Nrf2 in ovarian granulosa cells (GCs) has not been determined yet. Herein we aimed to study the function of Nrf2 in GCs. Human ovarian tissues were subjected to immunohistochemistry to localize Nrf2 and Keap1 and we detected the expression of Nrf2 and Keap1 in the human GCs...
October 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28963982/not-breathing-is-not-an-option-how-to-deal-with-oxidative-dna-damage
#19
REVIEW
Enni Markkanen
Oxidative DNA damage constitutes a major threat to genetic integrity, and has thus been implicated in the pathogenesis of a wide variety of diseases, including cancer and neurodegeneration. 7,8-dihydro-8oxo-deoxyGuanine (8-oxo-G) is one of the best characterised oxidative DNA lesions, and it can give rise to point mutations due to its miscoding potential that instructs most DNA polymerases (Pols) to preferentially insert Adenine (A) opposite 8-oxo-G instead of the correct Cytosine (C). If uncorrected, A:8-oxo-G mispairs can give rise to C:G→A:T transversion mutations...
September 22, 2017: DNA Repair
https://www.readbyqxmd.com/read/28903334/base-excision-repair-imbalance-in-colorectal-cancer-has-prognostic-value-and-modulates-response-to-chemotherapy
#20
Natalia M Leguisamo, Helena C Gloria, Antonio N Kalil, Talita V Martins, Daniel B Azambuja, Lisiane B Meira, Jenifer Saffi
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients' clinical and pathological features...
August 15, 2017: Oncotarget
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