TY - JOUR
T1 - Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes
AU - Aguilera-Aguirre, Leopoldo
AU - Hosoki, Koa
AU - Bacsi, Attila
AU - Radák, Zsolt
AU - Wood, Thomas G.
AU - Widen, Steven G.
AU - Sur, Sanjiv
AU - Ameredes, Bill T.
AU - Saavedra-Molina, Alfredo
AU - Brasier, Allan R.
AU - Ba, Xueqing
AU - Boldogh, Istvan
N1 - Funding Information:
This work was supported by Grants NIEHS RO1 ES018948 (IB), NIAID/AI062885 (ARB, IB), NHLBI Proteomic Center , N01HV00245 (IB, SS, Dr. A. Kurosky director); NIEHS Center Grant P30 ES006676 ; International Science-Technology Collaboration Foundation ( 20120728 ) of Jilin Province in China (XB), the European Union and the European Social Fund, TAMOP 4.2.2.A-11/1/KONV-2012–2023 (AB). L. Aguilera-Aguirre is an Environmental Toxicology Research Training Fellow (NIEHS T32 ES007254–22). We thank Mardelle Susman (Department of Microbiology and Immunology) for critically editing the manuscript and Dr. David Konkel (Institute for Translational Sciences, UTMB) both for his scientific input and for editing the manuscript. We also thank unknown reviewers for constructive comments that helped us to improve the quality of the manuscript.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
KW - 8-Oxoguanine
KW - Biological processes
KW - Gene expression
KW - OGG1-BER
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U2 - 10.1016/j.freeradbiomed.2015.01.004
DO - 10.1016/j.freeradbiomed.2015.01.004
M3 - Article
C2 - 25614460
AN - SCOPUS:84923699777
SN - 0891-5849
VL - 81
SP - 107
EP - 118
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -