title: 8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: German
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: David
authors.initials: D
authors.lastname: Saenz
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Szaniszlo
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Aguilera-Aguirre
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Lang
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Muralidhar L
authors.initials: ML
authors.lastname: Hegde
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Hajas
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radak
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Sankar
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: John
authors.initials: J
authors.lastname: Papaconstantinou
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. Electronic address: sboldogh@utmb.edu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D051379:Mice
chemical_list: D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C479058:oxoguanine glycosylase 1, human
keywords: 8-oxoguanine; Aging; OGG1; Senescence