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https://www.readbyqxmd.com/read/28542301/electronic-cigarette-aerosols-suppress-cellular-antioxidant-defenses-and-induce-significant-oxidative-dna-damage
#1
Vengatesh Ganapathy, Jimmy Manyanga, Lacy Brame, Dehra McGuire, Balaji Sadhasivam, Evan Floyd, David A Rubenstein, Ilangovan Ramachandran, Theodore Wagener, Lurdes Queimado
BACKGROUND: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. OBJECTIVE: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. METHODS: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay...
2017: PloS One
https://www.readbyqxmd.com/read/28496412/nitric-oxide-synthase-activity-correlates-with-ogg1-in-ozone-induced-lung-injury-animal-models
#2
Suqin Zhang, Jianhua Li, Yuqin Li, Yufeng Liu, Hongxiang Guo, Xiaoli Xu
Background: NO is an important cellular signaling molecule which is derived from L-arginine by nitric oxide synthase (NOS) and the effects of NOS signaling in lung injury is conflicting. The present study was designed to observe the effect of NOS and Arginase signaling in the occurrence and development of lung injury and its mechanism. Methods: An ozone-stressed lung injury animal model was established by exposure to 2.0 ppm O3 for 30 min every day for consecutive 12 day with or without the administration of NO precursor L-arginine or non-selective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28486105/chd4-has-oncogenic-functions-in-initiating-and-maintaining-epigenetic-suppression-of-multiple-tumor-suppressor-genes
#3
Limin Xia, Wenjie Huang, Marina Bellani, Michael M Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W Zhang, Li-Rong Yu, Huili Li, Cynthia A Zahnow, Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V Rassool, Stephen B Baylin
An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28460087/base-excision-repair-variants-and-pesticide-exposure-increase-parkinson-s-disease-risk
#4
Laurie H Sanders, Kimberly C Paul, Evan H Howlett, Hakeem Lawal, Sridhar Boppana, Jeff M Bronstein, Beate Ritz, J Timothy Greenamyre
Exposure to certain pesticides induces oxidative stress and increases Parkinson's disease (PD) risk. Mitochondrial DNA (mtDNA) damage is found in dopaminergic neurons in idiopathic PD and following pesticide exposure in experimental models thereof. Base excision repair (BER) is the major pathway responsible for repairing oxidative DNA damage in cells. Whether single nucleotide polymorphisms (SNPs) in BER genes alone or in combination with pesticide exposure influence PD risk is unknown. We investigated the contributions of functional SNPs in 2 BER genes (APEX1 and OGG1) and mitochondrial dysfunction- or oxidative stress-related pesticide exposure, including paraquat, to PD risk...
April 29, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28266569/ogg1-dna-interactions-facilitate-nf-%C3%AE%C2%BAb-binding-to-dna-targets
#5
Lang Pan, Wenjing Hao, Xu Zheng, Xianlu Zeng, Adeel Ahmed Abbasi, Istvan Boldogh, Xueqing Ba
DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5' or 3' guanine in runs of guanines to mimic oxidative effects...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28258190/sirt3-deficiency-promotes-lung-fibrosis-by-augmenting-alveolar-epithelial-cell-mitochondrial-dna-damage-and-apoptosis
#6
Renea P Jablonski, Seok-Jo Kim, Paul Cheresh, David B Williams, Luisa Morales-Nebreda, Yuan Cheng, Anjana Yeldandi, Sangeeta Bhorade, Annie Pardo, Moises Selman, Karen Ridge, David Gius, G R Scott Budinger, David W Kamp
Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis. Human lungs were assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD(K68) Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assayed by immunoblotting with or without SIRT3 enforced expression or silencing...
March 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28253266/association-of-ogg1-and-mthfr-polymorphisms-with-age-related-cataract-a-systematic-review-and-meta-analysis
#7
Xiaohang Wu, Weiyi Lai, Haotian Lin, Yizhi Liu
PURPOSE: To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC). METHODS: A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28242328/mitochondrial-transcription-factor-a-tfam-rs1937-and-ap-endonuclease-1-ape1-rs1130409-alleles-are-associated-with-reduced-cognitive-performance
#8
Meryl S Lillenes, Mari Støen, Clara-Cecilie Günther, Per Selnes, Vidar T V Stenset, Thomas Espeseth, Ivar Reinvang, Tormod Fladby, Tone Tønjum
Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer's disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28218666/the-ageing-brain-effects-on-dna-repair-and-dna-methylation-in-mice
#9
Sabine A S Langie, Kerry M Cameron, Gabriella Ficz, David Oxley, Bartłomiej Tomaszewski, Joanna P Gorniak, Lou M Maas, Roger W L Godschalk, Frederik J van Schooten, Wolf Reik, Thomas von Zglinicki, John C Mathers
Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#10
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159922/base-excision-repair-imbalance-in-colorectal-cancer-has-prognostic-value-and-modulates-response-to-chemotherapy
#11
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...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28150947/sequencing-the-mouse-genome-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine-by-og-seq
#12
Yun Ding, Aaron M Fleming, Cynthia J Burrows
Oxidative damage to the genome can yield the base 8-oxo-7,8-dihydroguanine (OG). In vitro studies suggested OG would preferentially form in 5'-GG-3' sequence contexts after exposure to reactive oxygen species. Herein, OG locations in the genome were studied by development of "OG-Seq" to sequence OG sites via next-generation sequencing at ∼0.15-kb resolution. The results of this study found ∼10 000 regions of OG enrichment in WT mouse embryonic fibroblasts and ∼18 000 regions when the OG repair glycosylase Ogg1 was knocked out...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#13
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#14
Aaron M Fleming, Yun Ding, Cynthia J Burrows
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex-forming sequences (PQS) in promoter-coding strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (VEGF) or endonuclease III-like protein 1 (NTHL1) genes...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129013/oxidative-dna-damage-and-reduced-expression-of-dna-repair-genes-role-in-primary-open-angle-glaucoma-poag
#15
Kuldeep Mohanty, Rima Dada, Tanuj Dada
BACKGROUND: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis. MATERIALS AND METHODS: The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA...
January 27, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28125528/mitochondrial-dna-damage-initiates-acute-lung-injury-and-multi-organ-system-failure-evoked-in-rats-by-intra-tracheal-pseudomonas-aeruginosa
#16
Yann-Leei Lee, Boniface Obiako, Olena M Gorodnya, Mykhaylo V Ruchko, Jamie L Kuck, Viktor M Pastukh, Glenn L Wilson, Jon D Simmons, Mark N Gillespie
Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal P. aeruginosa (strain 103; PA103)-induced ALI and MOSF...
January 25, 2017: Shock
https://www.readbyqxmd.com/read/28098999/dna-deformation-coupled-recognition-of-8-oxoguanine-conformational-kinetic-gating-in-human-dna-glycosylase
#17
Haoquan Li, Anton V Endutkin, Christina Bergonzo, Lin Fu, Arthur Grollman, Dmitry O Zharkov, Carlos Simmerling
8-Oxoguanine (8-oxoG), a mutagenic DNA lesion generated under oxidative stress, differs from its precursor guanine by only two substitutions (O(8) and H(7)). Human 8-oxoguanine glycosylase 1 (OGG1) can locate and remove 8-oxoG through extrusion and excision. To date, it remains unclear how OGG1 efficiently distinguishes 8-oxoG from a large excess of undamaged DNA bases. We recently showed that formamidopyrimidine-DNA glycosylase (Fpg), a bacterial functional analog of OGG1, can selectively facilitate eversion of oxoG by stabilizing several intermediate states, and it is intriguing whether OGG1 also employs a similar mechanism in lesion recognition...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28087410/repair-of-8-oxog-a-mismatches-by-the-mutyh-glycosylase-mechanism-metals-and-medicine
#18
REVIEW
Douglas M Banda, Nicole N Nuñez, Michael A Burnside, Katie M Bradshaw, Sheila S David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28079919/copper-oxide-nanoparticles-and-copper-sulphate-act-as-antigenotoxic-agents-in-drosophila-melanogaster
#19
Mohamed Alaraby, Alba Hernández, Ricard Marcos
The biological reactivity of metal and metal oxide nanomaterials is attributed to their redox properties, which would explain their pro- or anti-cancer properties depending on exposure circumstances. In this sense, copper oxide nanoparticles (CuONP) have been proposed as a potential anti-tumoral agent. The aim of this study was to assess if CuONP can exert antigenotoxic effects using Drosophila melanogaster as an in vivo model. Genotoxicity was induced by two well-known genotoxic compounds, namely potassium dichromate (PD) and ethyl methanesulfonate (EMS)...
January 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#20
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
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