A3shNT cell transcriptomics
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155782 | GEO | 2020/08/07
REPOSITORIES: GEO
Similar Datasets
Project description:Balb/cJ mouse received control RNAi or RNAi to 8-oxoguanine DNA glycosylase (Ogg1) intranasally prior to the exposure for 1 h to a) glucose oxidase (1 mU) to induce OGG1-BER or b) OGG1-BER product 8-oxoguanine (1 μM). We used SABiosciences Mouse Inflammatory Cytokines & Receptors PCR Array (PAMM-011A) to quantitate inflammatory gene expression dependent on OGG1 and its product 8-oxoguanine.
2014-08-26 | GSE60711 | GEO
Project description:Balb/cJ mouse received control RNAi or RNAi to 8-oxoguanine DNA glycosylase (Ogg1) intranasally prior to the exposure for 1 h to a) glucose oxidase (1 mU) to induce OGG1-BER or b) OGG1-BER product 8-oxoguanine (1 M-NM-<M). We used SABiosciences Mouse Inflammatory Cytokines & Receptors PCR Array (PAMM-011A) to quantitate inflammatory gene expression dependent on OGG1 and its product 8-oxoguanine. After intranasal challenge with glucose oxidase or 8-oxoguanine, mice were sacrificed and lungs were collected and processed to obtain RNA. Total pooled (n=5) RNA (1 M-NM-<g) was reverse transcribed into cDNA using SuperscriptM-BM-. III First Strand Synthesis System (Invitrogen), mixed with equal amounts of 2X SYBR Green Supermix (Qiagen) and 20 M-NM-<l of reaction mixture was added to each well of the PAM-011A array. The reaction was evaluated using an ABI PRISMM-BM-. 7000 Sequence Detection System using recommended settings by SABiosciences.
2014-08-26 | E-GEOD-60711 | biostudies-arrayexpress
Project description:Oxidative DNA damage is recognised by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1), initiating repair. Here, we describe a small molecule (TH10785) that interacts with the Phe319 and Gly42 amino acids of OGG1, increases the enzyme activity 10-fold and generates a novel β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and ageing.
2022-06-24 | GSE188779 | GEO
Project description:Purpose: The aim of this study is to evaluate the global gene expression induced by OGG1-BER product 8-oxoG in mouse airways. Methods: RNA extracted from individual mouse lungs (experimental group: n=5) were pooled and a total 1 M-NM-<g RNA was used for Next-Generation Sequencing (NGS) analyses on an Illumina HiSeq 1000 sequencing system. Sequence analysis were performed in duplicate. First- and second-strand synthesis, adapter ligation and amplification of the library were performed using the Illumina TruSeq Sample Preparation Kit as recommended by the manufacturer (Illumina). Library quality was evaluated by using an Agilent DNA-1000 chip on an Agilent 2100 Bioanalyzer. Library DNA templates were quantitated by qPCR using known reference starndards. Cluster formation of the library of DNA templates was performed using the TruSeq PE Cluster Kit v3 (Illumina) and the Illumina cBot workstation. Paired-end, 50-base sequencing was performed with a TruSeq SBS kit v3 (Illumina) on the Illumina HiSeq 1000 by protocols defined by the manufacturer. Base call conversion to sequence reads was performed using CASAVA-1.8.2. Sequence data were analyzed with the Bowtie2, Tophat2 and GFOLD programs. Processed data are presented as reads per kilobase transcript per million (RPKM), normalized to the experimental control (RNA from saline-challenged lungs) and reported as fold change (test/control). Results: We mapped an average of 24.76 million sequence reads per sample and identified 23,337 transcripts in total RNA extracted from lungs of Balb/cJ mice as described in Methods. Approximately 10% of the transcripts showed differential expression between the saline-challenged control and 8-oxoguanine-challeged mouse lungs, with a fold change M-bM-^IM-%3.0. We validated the expression changes of 7 selected pro-inflammatory cytokines and chemokines of interest for our studies by qRT-PCR. Hierarchical clustering followed by Protein ANalysis THrough Evolutionary Relationships database (PANTHER) analysis of differentially expressed genes. Results showed overrepresentation of various biological functions (GO terms) including immune system process (GO:0002376; p=5.24e-12) among others. Pathway analysis (PANTHER) indicated that the most overrepresented pathway was inflammation mediated by chemokine and cytokine (P00031, p=<0.01). In addition to gene expression analysis, we confirmed OGG1M-bM-^@M-"8-oxoG-dependent RAS activation in lungs by active RAS pull-down assays, airways neutrophil accumulation by bronchoalveolar lavage fluid (BALF) differential cell counts and airway inflammation by histological examination (H&E staining) of lung sections. Conclusions: This is the first study at the whole-transcriptome level to show induction of innate immune response gene expression in mouse lungs after exposure to OGG1-BER product 8-oxoG. Balb/cJ mice (5 per group) were intranasally challenged with 8-oxoguanine (1 M-BM-5M, 60 M-BM-5l) for 30, 60 and 120 min. Control group mice were intranasally challenged with saline (60 M-BM-5l). RNA from individual mice whithin the same group was pooled and subjected to deep-sequencing analysis in duplicate using NGS on an Illumina HiSeq 1000 sequencing system. After alignment and processing, the resulting RPKM from treatment groups (8-oxoG-challenged) were normalized to the control group (saline-challenged).
2015-02-02 | E-GEOD-61095 | biostudies-arrayexpress
Project description:Unrepaired DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair activity to stave off age-associated functional decline remain obscure. Here, we show that histone deacetylase 1 (HDAC1) modulates DNA repair in the aging brain via targeting OGG1 of the base excision repair pathway. Mice deficient in HDAC1 display age-associated accumulation of DNA damage in the brain and cognitive impairment. HDAC1 interacts with and positively stimulates OGG1, a DNA glycosylase that primarily acts on 8-oxoguanine (8-oxoG), a type of oxidative DNA damage associated with transcriptional repression. Loss of HDAC1 leads to impaired OGG1 activity, 8-oxoG accumulation at the promoters of a subset of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG lesions along with reduced HDAC1 activity and downregulation of a similar set genes in the 5XFAD mouse model of Alzheimer’s disease (AD). Notably, pharmacological activation of HDAC1 confers protection against the deleterious effects of 8-oxoG lesions in the brains of aged wild-type and 5XFAD mice. Our work uncovers an important role for HDAC1 in the repair of 8-oxoG lesions and highlights HDAC1 activation as a novel therapeutic strategy to counter functional decline during brain aging and neurodegeneration.
2020-03-30 | GSE115437 | GEO
Project description:Reactive oxygen species (ROS) induced by ultraviolet B (UVB) cause DNA damage such as 8-oxoguanine (8-oxoG) in mouse skin, with long-term exposure leading skin tumor development. We previously reported that Ogg1 knockout mice, with defective repair enzyme for 8-oxoG oxidatively damaged DNA, showed greater up-regulation of inflammatory response genes and Versican, which encodes a large extracellular matrix proteoglycan, than their wild-type counterparts. Here, we focused on inflammatory response genes associated with Versican up-regulation after UVB exposure, using Ogg1 knockout mouse embryonic fibroblasts (MEFs). Gene profiling among inflammatory response-associated genes in MEFs treated with UVB showed that Cxcl1, a CXC chemokine, was most significantly up-regulated in Ogg1(-/-) MEFs, concomitant with the up-regulation of Versican. We found that Versican targeted siRNA directly regulated Cxcl1, and vice versa, in which the system of up-regulation for these two key genes were controlled by PI3kinase-NFkB activation signaling rather than conventional UV-induced p38 mitogen-activated protein kinase. Furthermore, for the initial process of differentiating inflammatory response between Ogg1(-/-) and Ogg1(+/+), we found that down-regulation of p53 along with anti-apoptotic signal was a key event in Ogg1(-/-).The results of the present study suggest suppression of skin tumor development involving UVB/ROS-induced 8-oxoG formation by targeting genes and signaling pathways.
2016-04-25 | GSE80362 | GEO
Project description:Purpose: The aim of this study is to test whether global gene expression induced by multiple challenges with OGG1-BER product 8-oxoG in mouse airways is linked to airway remodeling. Methods: RNAs extracted from individual mouse lungs (experimental group: n=5) were pooled and a total 1 ?g RNA was used for Next-Generation Sequencing (NGS) analyses on an Illumina HiSeq 1000 sequencing system. Sequence analyses were performed in duplicate. First- and second-strand synthesis, adapter ligation and amplification of the library were performed using the Illumina TruSeq Sample Preparation Kit as recommended by the manufacturer (Illumina). Library quailty was evaluated by using an Agilent DNA-1000 chip on an Agilent 2100 Bioanalyzer. Library DNA templates were quantitated by qPCR using known reference standards. Cluster formation of the library of DNA templates was performed using the TruSeq PE Cluster Kit v3 (Illumina) and the Illumina cBot workstation. Paired-end, 50-base sequencing was performed with a TruSeq SBS kit v3 (Illumina) on the Illumina HiSeq 1000 by protocols defined by the manufacturer. Base call conversion to sequence reads was performed using CASAVA-1.8.2. Sequence data were analyzed with the Bowtie2, Tophat2 and GFOLD programs. Processed data are presented as reads per kilobase transcript per million (RPKM), normalized to the experimental control (RNA from saline challenged lungs) and reported as fold change (test/control). Results: We mapped an average of 31.41 million sequence reads per sample and identified 23,337 transcripts in total RNA extracted from lungs of Balb/cJ mice as described in Methods. Approximately 14% of the transcripts showed differential expression between the saline-challenged control and 8-oxoguanine-challeged mouse lungs, with a fold change ?3.0. We validated the expression changes of 18 selected EMT-related genes of interest for our studies by qRT-PCR. Hierarchical clustering followed by Protein ANalysis THrough Evolutionary Relationships database (PANTHER) analysis of differentially expressed genes was done using GENE-E online software from Broad Institute (http://www.broadinstitute.org/cancer/software/GENE-E/). Results from PANTHER analysis of upregulated transcripts (fold change ?3.0) showed overrepresentation of various biological functions (GO terms) including developmental process (GO:0032502, P=4.58E-33), system development (GO:0048731, P=9.16E-33), cellular process (GO:0009987, P= 5.52E-31), cell adhesion (GO:0007155, P= 8.63E-28) among others. Pathway analysis (PANTHER) indicated that the most overrepresented pathways were: cadherin signaling (P00012, P=6.62E-07), wnt signaling (P00057, P= 5.81E-06), integrin signaling (P00034, P= 1.09E-05) among others. In addition to gene expression analysis, we confirmed airway remodeling by histological examination (Hematoxylin and Eosin, Masson's trichrome staining) of lung sections at seven days from the last challenge (day 11). Conclusions: This is the first study showing a link between gene expression at whole-transcriptome level induced by chronic OGG1-BER (mimicked by multiple challenges with 8-oxoG) and airway remodeling, supported by histological structural changes in lungs. Balb/cJ mice (5 per group) were intranasally challenged with 8-oxoguanine (1 µM, 60 µl) for three times at days 0, 2 and 4. Control group mice were intranasally challenged with saline (60 µl). At 30, 60 and 120 min after the third challenge (day 4), mice were sacrificed and lungs were processed for RNA extraction. RNAs from individual mice within the same group were pooled and subjected to deep-sequencing analysis in duplicate using NSG on an Illumina HiSeq 1000 sequencing system. After alignment and processing, the resulting RPKM from treatment groups (8-oxoG-challenged) were normalized to control group (saline-challenged).
2015-07-03 | E-GEOD-65031 | biostudies-arrayexpress
Project description:We report the application of ChIP-Sequencing for profiling genome-wide distribution of 8-oxoguanine DNA glycosylase (OGG1) which is a DNA base excision repair protein, after TNF exposure of cells. By obtaining an average of over 18 million of total reads per sample and over 19.5 million of unique reads per sample from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HEK293 cells. We performed gene ontology and functional pathway analysis of genes associate with peaks, and identify regions of the genomes (e.g. promoter, introns, etc) where the peaks tend to occur. The results show that OGG1 is primarily associated with promoter regions in vicinity of transcription factor binding sites 5' of transcription start sites (TSS). This pattern of distribution occurs in spite of genome-wide oxidative modifications of guanine (primarily 8-oxoG). OGG1 increased highly significant (1e-09 to 1e-517) enrichment of 57 transcription factor binding sites including those for Sox(2, 3, 6, 10), RUNX, RUNX(1, 2), HOX(C, D), STAT(1, 3, 6), IRF(1 to 4), NF-κB. In controls, the DNA was chromatin immunoprecipitated using antibody to NF-κB/RelA. These and other data derived from further analysis, suggest that OGG1 modulates binding of transcription factors and gene expression.
2018-07-15 | GSE75562 | GEO
Project description:We report the application of ChIP-Sequencing for profiling genome-wide distribution of 8-oxoguanine DNA glycosylase1 (OGG1, a DNA base excision repair protein), after oxidative stress exposure mediated by glucose oxidase (GOx) of cells. By obtaining an average of over 18 million of total reads per sample and over 19.5 million of unique reads per sample from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HEK293 cells. We performed gene ontology and functional pathway analysis of genes associated with peaks to identify regions of the genomes (e.g. promoter, introns, etc) where the peaks tend to occur. The results show that OGG1 is primarily associated with promoter regions in vicinity of transcription factor binding sites 5' of transcription start sites (TSS). This pattern of distribution occurs in spite of genome-wide oxidative modifications of guanines (primarily 8-oxoG). OGG1 increased significantly at regulatory regions of CXC-, CC- chemokines, cytokines and growth factors. In controls, the DNA was chromatin immunoprecipitated using antibody to NF-κB/RelA. As expected NF-κB was enriched on gene regulatory regions including those of proinflammatory,cell proliferation ones. These and other data derived from further analysis, suggest that OGG1 modulates gene expression in coordination with NF-κB.
2018-07-06 | GSE89017 | GEO
Project description:Aging is accompanied by a decline in DNA repair efficiency, which leads to the accumulation of different types of DNA damage. Age-associated chronic inflammation and generation of reactive oxygen species exacerbate the aging process and age-related chronic disorders. These inflammatory processes establish conditions that favor accumulation of DNA base damage, especially 8-oxo-7,8 di-hydroguanine (8-oxoG), which in turn contributes to various age associated diseases. 8-oxoG is repaired by 8-oxoG glycosylase1 (OGG1) through the base excision repair (BER) pathway. OGG1 is present in both the cell nucleus and in mitochondria. Mitochondrial OGG1 has been implicated in mitochondrial DNA repair and increased mitochondrial function. Using transgenic mouse models and cell lines that have been engineered to have enhanced expression of mitochondria-targeted OGG1 (mtOGG1), we show that elevated levels of mtOGG1 in mitochondria can reverse aging-associated inflammation and improve functions. Old male mtOGG1Tg mice show decreased inflammation response, decreased TNFα levels and multiple pro-inflammatory cytokines. Moreover, we observe that male mtOGG1Tg mice show resistance to STING activation. Interestingly, female mtOGG1Tg mice did not respond to mtOGG1 overexpression. Further, HMC3 cells expressing mtOGG1 display decreased release of mtDNA into the cytoplasm after lipopolysacchride induction and regulate inflammation through the pSTING pathway. Also, increased mtOGG1 expression reduced LPS-induced loss of mitochondrial functions. These results suggest that mtOGG1 regulates age-associated inflammation by controlling release of mtDNA into the cytoplasm. To understand what metabolism-related gene expression changes are altered in mice overexpressing a mitochondrial OGG1 enzyme. Hippocampi tissues were collected from 13 month old control and transgenic mouse and subjected to RNA isolation.
2023-06-14 | GSE227426 | GEO