Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity

Jensen, Annie Aarup; Løhr, Mille; Eriksen, Louise; Grønbæk, Morten; Dorry, Elad; Loft, Steffen; Möller, Peter

doi:10.1016/j.freeradbiomed.2011.09.038

Cited by 44 publications

(26 citation statements)

References 51 publications

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“…We usually find substantially higher levels of FPG-sensitive sites than of hOGG1-sensitive sites in human PBMC samples, although the levels of FPG-and hOGG1-sensitive sites are similar and high after treatment with the photosensitizer Ro19-8022 or potassium bromate inducing specifically 8-oxodG [16][17][18].…”

Section: Collection and Analysis Of Biomarker Samplesmentioning

confidence: 84%

Controlled exposure to diesel exhaust and traffic noise – Effects on oxidative stress and activation in mononuclear blood cells

Hemmingsen

Möller

Jantzen

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Section: Collection and Analysis Of Biomarker Samplesmentioning

confidence: 84%

Controlled exposure to diesel exhaust and traffic noise – Effects on oxidative stress and activation in mononuclear blood cells

Hemmingsen

Möller

Jantzen

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…Such studies suggest that oxidative stress is a mechanism by which cellular microenvironments inactivate S326C-OGG1 and thereby contribute to tumorigenesis. In S326C- Ogg1 heterozygous blood cells, increased DNA damage has been measured (52), suggesting that even a single allele of S326C- Ogg1 may be sufficient to cause decreased 8-oxodG repair capacity. One contributor to the association between S326C- Ogg1 and tumorigenesis may be loss of heterozygosity (LOH) (53), which is one of the most common DNA alterations in cancer (54).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

et al. 2015

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Reactive oxygen species threaten genomic integrity by inducing oxidative DNA damage. One common form of oxidative DNA damage is the mutagenic lesion 8-oxoguanine (8-oxodG). One driver of oxidative stress that can induce 8-oxodG is inflammation, which can be initiated by the cytokine tumor necrosis factor alpha (TNF-α). Oxidative DNA damage is primarily repaired by the base excision repair pathway, initiated by glycosylases targeting specific DNA lesions. 8-oxodG is excised by 8-oxoguanine glycosylase 1 (OGG1). A common Ogg1 allelic variant is S326C-Ogg1, prevalent in Asian and Caucasian populations. S326C-Ogg1 is associated with various forms of cancer, and S326C-OGG1 is inactivated by oxidation. However, whether oxidative stress caused by inflammatory cytokines compromises OGG1 variant repair activity remains unknown. We addressed whether TNF-α causes oxidative stress that both induces DNA damage and inactivates S326C-OGG1 via cysteine 326 oxidation. In mouse embryonic fibroblasts, we found that S326C-OGG1 was inactivated only after exposure to H2O2 or TNF-α. Treatment with the antioxidant N-acetylcysteine prior to oxidative stress rescued S326C-OGG1 activity, demonstrated by in vitro and cellular repair assays. In contrast, S326C-OGG1 activity was unaffected by potassium bromate, which induces oxidative DNA damage without causing oxidative stress, and presumably cysteine oxidation. This study reveals that Cys326 is vulnerable to oxidation that inactivates S326C-OGG1. Physiologically relevant levels of TNF-α simultaneously induce 8-oxodG and inactivate S326C-OGG1. These results suggest a mechanism that could contribute to increased risk of cancer among S326C-Ogg1 homozygous individuals.

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“…OGG1 involves in repair of oxidative DNA damage [11, 12]. Dysregulation or loss of OGG1 causes accumulation of oxidative DNA damage [13-15], which is strongly associated with various diseases, including cancer [16]. OGG1 polymorphism have been reported to associate to susceptibility of lung cancer[17-20], pancreatic cancer [21-24], bladder cancer [25-28], breast cancer [29-31], esophageal cancer, colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1

Huang

Shi

Huang

et al. 2017

Cell Physiol Biochem

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Background: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5’,6,6’-Tetrachloro-1,1’,3,3’-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2’,7’-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. Results: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3’UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to ‘CUGUUGA’ in 3’UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. Conclusion: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

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Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity

Cited by 44 publications

References 51 publications

Controlled exposure to diesel exhaust and traffic noise – Effects on oxidative stress and activation in mononuclear blood cells

Controlled exposure to diesel exhaust and traffic noise – Effects on oxidative stress and activation in mononuclear blood cells

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1

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