Article ID Journal Published Year Pages File Type
1907822 Free Radical Biology and Medicine 2015 12 Pages PDF
Abstract

Reactive oxygen species inflict oxidative modifications on various biological molecules, including DNA. One of the most abundant DNA base lesions, 8-oxo-7,8-dihydroguanine (8-oxoG) is repaired by 8-oxoguanine DNA glycosylase-1 (OGG1) during DNA base excision repair (OGG1-BER). 8-OxoG accumulation in DNA has been associated with various pathological and aging processes, although its role is unclear. The lack of OGG1-BER in Ogg1−/− mice resulted in decreased inflammatory responses and increased susceptibility to infections and metabolic disorders. Therefore, we proposed that OGG1 and/or 8-oxoG base may have a role in immune and homeostatic processes. To test our hypothesis, we challenged mouse lungs with OGG1-BER product 8-oxoG base and changes in gene expression were determined by RNA sequencing and data were analyzed by Gene Ontology and statistical tools. RNA-Seq analysis identified 1592 differentially expressed (≥ 3-fold change) transcripts. The upregulated mRNAs were related to biological processes, including homeostatic, immune-system, macrophage activation, regulation of liquid-surface tension, and response to stimulus. These processes were mediated by chemokines, cytokines, gonadotropin-releasing hormone receptor, integrin, and interleukin signaling pathways. Taken together, these findings point to a new paradigm showing that OGG1-BER plays a role in various biological processes that may benefit the host, but when in excess could be implicated in disease and/or aging processes.

Graphical abstractProposed model for activation of biological processes by OGG1-BER. OGG1, 8-oxoguanine DNA glycosylase-1; 8-oxoG, the base 8-oxo-7,8-dihydroguanine; 8-oxodG, 8-oxo-7,8-dihydrodeoxyguanosine.Figure optionsDownload full-size imageDownload high-quality image (139 K)Download as PowerPoint slide

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Life Sciences Biochemistry, Genetics and Molecular Biology Ageing
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