Biochemical identification of a hydroperoxide derivative of the free 8-oxo-7,8-dihydroguanine base

Hajas, György; Bácsi, Attila; Aguilerra-Aguirre, Leopoldo; Germán, Péter; Radák, Zsolt; Sur, Sanjiv; Hazra, Tapas K.; Boldogh, István

doi:10.1016/j.freeradbiomed.2011.11.015

Cited by 14 publications

(14 citation statements)

References 44 publications

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“…Therefore, we speculate that multiple 8-oxoG challenge-induced changes in gene expression primarily represent the response of the airway epithelium with the possible contribution of subjacent cells. In support of this idea, (a) 8-oxoG is rapidly taken up by cells [57], possibly by the lung epithelium; (b) small GTPases were activated from 15 min on; and (c) robust changes in gene expression were observed from 30 min on (60 min maximum) [20, 46]. The question still remains of how histological changes occur in subepithelial regions.…”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling

Aguilera-Aguirre

Hosoki

Bácsi

et al. 2015

Free Radical Biology and Medicine

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Reactive oxygen species (ROS) generated by environmental exposures, and endogenously as by-products of respiration, oxidatively modify biomolecules including DNA. Accumulation of ROS-induced DNA damage has been implicated in various diseases that involve inflammatory processes, and efficient DNA repair is considered critical in preventing such diseases. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base-excision repair (OGG1-BER) pathway. Recent studies have shown that the OGG1-BER byproduct 8-oxoG base forms a complex with cytosolic OGG1, activating small GTPases and downstream cell signaling in cultured cells and lungs. This implies that persistent OGG1-BER could result in signaling leading to histological changes in airways. To test this, we mimicked OGG1-BER by repeatedly challenging airways with its repair product 8-oxoG base. Gene expression was analyzed by RNA sequencing (RNA-Seq) and qRT-PCR, and datasets were evaluated by gene ontology and statistical tools. RNA-Seq analysis identified 3252 differentially expressed transcripts (2435 up- and 817 downregulated, Z3-fold change). Among the upregulated transcripts, 2080 mRNAs were identified whose encoded protein products were involved in modulation of the actin family cytoskeleton, extracellular matrix, cell adhesion, cadherin, and cell junctions, affecting biological processes such as tissue development, cell-to-cell adhesion, cell communication, and the immune system. These data are supported by histological observations showing epithelial alterations, subepithelial fibrosis, and collagen deposits in the lungs. These data imply that continuous challenge by the environment and consequent OGG1-BER-driven signaling trigger gene expression consistent with airway remodeling.

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Section: Discussionmentioning

confidence: 99%

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling

Aguilera-Aguirre

Hosoki

Bácsi

et al. 2015

Free Radical Biology and Medicine

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“…In the first stage of the process an electron from a molecule of guanine is abstracted with the participation of a hydroxyl radical (the abstraction of an electron can also be an effect of quantum radiation or some other equally strong attack, by an oxidant such as a ferrous radical 15 , or as a result of the reaction of type I photosensitizers). [16][17][18][19] In the second stage of the reaction, the final product is formed (Fig. 4).…”

Section: -Hydroxy-2'-deoxyguanosinementioning

confidence: 99%

Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage

Dąbrowska¹,

Wiczkowski²

2017

Adv Clin Exp Med

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Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when present in excess. Pathological changes within cells and tissues can result from a persistent excess of free radicals. Living organisms are increasingly exposed to oxidative stress, resulting in oxidative DNA modifications. One such modification is 8-hydroxy-2'-deoxyguanosine (8-OHdG). It is considered a biomarker of oxidative stress and oxidative DNA damage. It has been found both in physiological fluids and in cells. This paper presents methods found in the literature for determining 8-OHdG expression in various kinds of biological material -blood, urine or liver homogenates. Methods for determining the biomarker expression have been grouped into direct and indirect methods, and the various levels of 8-hydroxy-2'-deoxyguanosine that can be determined by the different techniques are presented. The basic pros and cons of the various techniques are also discussed.

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“…Studies have also demonstrated that when free 8-oxoG base released from genome or added to cells [which rapidly enter into cells (Hajas et al, 2012)] it is bound by OGG1 with high affinity, and the resulting complex (OGG1•8-oxoG) physically interacts with small GTPases (Boldogh et al, 2012). Importantly, the OGG1•8-oxoG complex caused GDP → GTP exchange in Kirsten (K)-RAS, neuroblastoma RAS viral oncogene homolog (N)-RAS, Harvey (H)-RAS, RHOA and RHO family member RAC1 (Aguilera-Aguirre et al, 2014; Boldogh et al, 2012) and thus it functions as a guanine nucleotide exchange factor (GEF) in a manner similar to that of other GEFs (Mosteller et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Germán

Saenz

Szaniszlo

et al. 2017

Mechanisms of Ageing and Development

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Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed --86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

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Biochemical identification of a hydroperoxide derivative of the free 8-oxo-7,8-dihydroguanine base

Cited by 14 publications

References 44 publications

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling

Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

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