BACKGROUND: The effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC.
METHODS: We analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues.
RESULTS: In ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1.
CONCLUSIONS: In populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai\'an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.

Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.

It has been reported that oxidative stress and chronic inflammation may be involved in the pathogenesis of polycystic ovary syndrome (PCOS). 8-oxoguanine DNA glycosylase (OGG1) is the main glycosylase that catalyzes the excision of DNA oxidation products. In this study, we investigated the role and potential mechanisms of OGG1 in the development of PCOS. We first analyzed OGG1 levels in serum and follicular fluid (FF) of PCOS patients, and significantly elevated OGG1 levels were noted in PCOS patients. We similarly observed a significant upregulation of OGG1 expression levels in ovarian tissue of the dehydroepiandrosterone (DHEA)-induced PCOS rat model. In addition, increased apoptosis and increased production of reactive oxygen species (ROS) were observed after the addition of OGG1-specific inhibitor (TH5487) in human granulosa-like tumor cell line (KGN) cells following a concentration gradient, along with a significant decrease in mRNA levels of inflammatory factors such as CXCL2, IL-6, MCP1, IL-1β, and IL-18. Significant decreases in protein phosphorylation levels of P65 and IκBα were also observed in cells. In addition, we found a significant positive correlation between OGG1 and IL-6 expression levels in human and DHEA-induced PCOS rat models. In conclusion, our results suggest that OGG1 might be involved in the pathogenesis of PCOS by regulating the secretion of IL-6 through NF-κB signaling pathway, and there might be a balance between the inhibition of oxidative stress and the promotion of chronic inflammation by OGG1 on KGN cells.

Oxidative/antioxidant imbalance is considered a causal cause of diminished ovarian reserve (DOR). 8-oxyguanine DNA glycosylase (OGG1) has been reported to act as an antioxidant by binding non-catalytically to oxidation-induced DNA damage in the promoter region.
This study aimed to evaluate serum OGG1 concentrations in patients with or without DOR and to explore the clinical value of OGG1 as a novel diagnostic indicator for DOR.
Sixty-four women with DOR and seventy-eight women with normal ovarian reserve (NOR) from the reproductive medical center of Renmin Hospital of Wuhan University were included. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine serum OGG1 levels in patients on 2-5 days of the menstrual cycle. Data regarding the enrolled patients were also obtained from the database of the hospital, including age, body mass index (BMI), anti-Müllerian hormone (AMH), etc. Results: OGG1 levels were increased in the DOR group (2.08 ± 0.70 vs 1.46 ± 0.47 nmol/L, P < 0.001) and negatively correlated with AMH levels (Spearman r = -0.586, P < 0.001). After adjusting for age and BMI, a negative association between OGG1 and AMH remained (β = -0.619, P < 0.001). ROC curve analysis showed that a cut-off value of 1.765 nmol/L had an appropriate sensitivity (81.30%) and specificity (76.90%) for discriminating individuals with and without DOR, with the area under the curve (95% CI) of 0.870 (0.814 to 0.926), P < 0.001.
We determined that serum OGG1 levels might be suggested as a new diagnostic indicator for DOR.

In situ imaging the repair activity of 8-oxoguanine (8-OG) DNA glycosylase in living cells is important as it is associated with genetic mutation. However, the existing imaging methods confront the interference of intracellular nuclease and resulting in false positive signal. Here, a closing-upon-repair DNA tetrahedron nanoswitch (CRTN) was designed for FRET imaging the repair activity of 8-OG DNA glycosylase in living cells with high specificity and accuracy. CRTN comprised a DNA tetrahedron, a recognition strand modified with 8-OG bases, and a reporting strand designed as hairpin structure and labeled with Cy3/Cy5 dual fluorophores. Initially, the DNA tetrahedron was linked with the reporting strand hybridized to the recognition strand, separating the Cy3 donor and Cy5 acceptor into FRET-invalid distance. Upon repair the 8-OG bases by 8-OG DNA glycosylase, CRTN could undergo a structure change from the open to closed state. Specifically, the reporting strand was dissociated from the recognition strand under the action of 8-OG DNA glycosylase and folded into hairpin structure, bringing the Cy3 donor and Cy5 acceptor into FRET-valid proximity with the generation of FRET signal, which could prevent false positive signal arising from nuclease degradation. CRTN exhibited the feasibility for detecting 8-OG DNA glycosylase activity in vitro with good sensitivity and selectivity. More importantly, CRTN could enter cells without any transfection for FRET imaging the repair activity of intracellular 8-OG DNA glycosylase with high specificity and accuracy. This approach provided a promising tool for deeper understanding 8-OG DNA glycosylase function and further studying genetic mutation-related diseases.

8-oxoguanine DNA glycosylase (OGG), which plays a crucial role in base excision repair (BER), is an important biomarker. The existing highly sensitive fluorescent methods always need complicated amplification design. The method with high sensitivity and simple design at the same time is urgently needed. Here, we developed a highly sensitive detection method for OGG detection with lambda exonuclease and the background signal suppression probe. Through probe structure design, the steric hindrance and competitive binding effects successfully suppressed the background signal. We achieved sensitive detection of OGG with a simple design, and the limit of detection was 5.0 × 10-4 U mL-1. Moreover, the method was highly selective and successfully applied to OGG detection in biological samples, which shows the potential clinical application value.

8-Oxoguanine DNA glycosylase (OGG1) is an important enzyme that plays a key role in oxidative DNA damage repair. OGG1 can specifically recognize and excise 8-oxoG (a product of oxidative damage found in double-stranded DNA) through base excision repair (BER). OGG1 is expressed in normal tissues, and in most tumor tissues. Oxidative cellular damage can produce an inflammatory reaction, alleviating some measure of constitutive OGG1 inhibition. OGG1 inhibition in cancer cells shows some promise as a new method of cancer treatment. Most current OGG1 research focuses on regulating OGG1 with targeted small molecules. To date, no aptamer screen for OGG1 has been reported. Aptamers are single-stranded DNA (ssDNA) or RNA oligonucleotides that can bind to a target with high affinity and specificity in vitro, that can be identified by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers can be used as chemical ligands to regulate intermolecular interactions. In this study, a screen for aptamers with OGG1 affinity was performed for the first time. Capillary electrophoresis (CE) is a microanalytical technique that offers speed and high separation efficiency. In this work, two screening methods based on CE-SELEX technology were established: a one-round pressure controllable selection, and a multi-round selection. The most important criterion for successful one-round pressure controllable selection is to select a competitive target with a different CE migration time than that of the target of interest. We mixed OGG1 with a competitive target and a nucleic acid library for CE analysis. Two proteins competitively bind sequences in the library, forming independent complexes. The concentration of the competitive target is continuously increased until complexes with the target stop decreasing, indicating that the target and the ssDNA library have formed a stable complex. Complexes were collected for PCR amplification, purification, and high-throughput sequencing to obtain high affinity aptamers. This method greatly improves screening efficiency, and reduces non-specific binding to the target, which is helpful for obtaining aptamers with high affinity and specificity. One-round pressure controllable selection for high affinity OGG1 selective aptamers was performed using single strand binding protein (SSB) to competitively and tightly bind nucleic acids in the library. The competitive screening pressure was increased by increasing the SSB concentration to eliminate sequences with low affinity for OGG1 from the random oligonucleotide library. Nucleic acid sequences with high OGG1 affinity were obtainable in one step, and OGG1-ssDNA complexes were collected by creating a timed program on Beckman P/ACE MDQ capillary electrophoresis. Collection occurred from 2.2 to 2.8 min. Under identical incubation and electrophoresis conditions, multiple round selections were conducted by injecting samples of co-incubated nucleic acid library and target into the capillary. After separation under a high-voltage electric field, nucleic acid target complexes were collected, amplified by PCR, purified, and used as an enriched secondary library in the next round of screening. High affinity aptamers were generally obtained within three rounds. Comparing results of the two screening methods, the three candidate aptamer sequences found with the highest frequency were consistent, and displayed KD values ranging from 1.71 to 2.64 μmol/L. Molecular docking analysis suggests that Apt 1 may bind to the OGG1 active pocket, which functions to repair oxidative damage. Comparison of the two screening methods indicates that one-round pressure controllable selection is more rapid and efficient, providing guidance for the design of other protein aptamer screening methods. The obtained aptamer is expected to be function effectively as an OGG1-mediated DNA repair inhibitor.

Natural killer/T-cell lymphoma (NKTCL) is an aggressive Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma with poor prognosis. In this study, we aimed to investigate the potential mechanism of latent membrane protein 1 (LMP1)-mediated tumorigenesis and provide a novel therapeutic strategy for targeting the EBV DNA genome. We found that LMP1 upregulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1β (PGC1β) through activation of nuclear factor-κB (NF-κB). Furthermore, the activated PGC1β upregulated the expression of 8-oxoguanine DNA glycosylase (OGG1) through the coactivation of nuclear respiratory factor 1 (NRF1) and GA-binding protein α (GABPα), preventing reactive oxygen species (ROS)-mediated base incision in the EBV genome and favoring its survival. Interruption of hexokinase domain component 1 (HKDC1) by either shRNA or Tf-D-HKC8 peptide suppressed the interaction of HKDC1 with voltage-dependent anion channel 1 (VDAC1), triggering mitochondrial dysfunction and excessive generation of ROS, thus resulting in EBV suppression through ROS-mediated DNA damage. Suppression of the EBV genome inhibited the expression of the LMP1/PGC1β/HKDC1/OGG1 signaling pathway, forming a positive feed forward loop for the generation of ROS, hence inhibiting the EBV genome and subsequent EBV-associated tumor development. We concluded that LMP1 triggers EBV-associated tumorigenesis through activation of the PGC1β pathway. This study provided a novel therapeutic strategy for the treatment of EBV-associated tumors by targeting HKDC1.

Previous publications have indicated that polycyclic aromatic hydrocarbons (PAHs) exposures are associated with increased DNA damage and abnormal cell cycle arrest; however, the details of mechanisms remain largely unknown. This study aimed to quantify the associations of 8-oxoguanine DNA glycosylase (OGG1) methylation with urinary PAHs metabolites, DNA damage and cell cycle arrest, and further to assess the role of OGG1 methylation in mediating the association of urinary PAHs metabolites with DNA damage and cell cycle arrest. Urinary biomarkers of PAHs exposure and a marker of oxidative DNA damage (8-hydroxy-2\'-deoxyguanosin, 8-OHdG) were measured by high performance liquid chromatography. Cell cycle of lymphocyte was analysed with flow cytometry and OGG1 methylation in venous blood was measured by pyrosequencing. After adjusting for covariates, urinary 1-OHP levels were positively associated with lymphocyte S phase arrest and oxidative DNA damage, while were negatively associated with G0/G1 phase arrest. OGG1 methylation was not only positively correlated with urinary 1-OHP in a dose-responsive manner (P trend = 0.008) but was also associated with G0/G1 phase arrest (OR: 0.63, 95% CI: 0.41-0.97), S phase arrest (OR: 1.55, 95% CI: 1.01-2.40) and oxidative DNA damage (OR: 1.71, 95% CI: 1.02-2.86). Mediation analysis estimated that OGG1 methylation mediated about 20% of associations between urinary 1-OHP levels and cell cycle arrest and oxidative DNA damage, respectively (all P < 0.05). Our findings suggested that urinary 1-OHP concentrations were associated with cell cycle arrest and oxidative DNA damage by a mechanism partly involving OGG1 methylation.

OBJECTIVE: To investigate the association between the 8-oxoguanine DNA glycosylase (OGG1) gene Ser326Cys (rs1052133) polymorphism and age-related cataract (ARC).
METHODS: MEDLINE and EMBASE were searched to identify potential studies published before May 19, 2017, investigating the association between the OGG1 gene Ser326Cys polymorphism and ARC risk. The quality of eligible studies was assessed using the Newcastle-Ottawa Scale tool. The association between the OGG1 gene Ser326Cys polymorphism and ARC was analyzed using meta-analysis. Publication bias and sensitivity analyses were also performed.
RESULTS: Six studies were included in this systematic review, and five of these studies with Hardy-Weinberg equilibrium were included in a meta-analysis. The sample size of the meta-analysis was 3716, including 1831 patients with cataract and 1885 controls. Odds ratios (ORs) were 0.67 (95% confidence interval (CI) 0.52-0.85), 0.90 (95% CI 0.54-1.51), 0.52 (95% CI 0.32-0.85) and 0.72 (95% CI 0.56-0.92) for recessive, dominant, additive and allele contrast models, respectively. Sensitivity analysis indicated that the results of the meta-analysis were robust. No publication bias was observed.
CONCLUSIONS: The OGG1 gene Ser326Cys polymorphism was associated with ARC risk.