title: Antioxidant up-regulation and increased nuclear DNA protection play key roles in adaptation to oxidative stress in epithelial cells.
abstract: Cells are armed with a vast repertoire of antioxidant defense mechanisms to help prevent the accumulation of oxidative damage. It is becoming increasingly apparent that the cellular adaptive response has an important antioxidant function to counteract oxidative stress. To investigate this adaptive response we assessed the effect of sublethal H2O2 on cell viability, enzymatic activity, and nuclear (nDNA) and mitochondrial DNA (mtDNA) susceptibility to damage and repair in cultured human retinal pigment epithelium (RPE) cells. This nondividing cell type exists in a highly oxidizing microenvironment in vivo. Prior exposure to sublethal H2O2 confirmed an adaptive response, resulting in a greater cellular resistance to subsequent toxic exposures compared to nonadapted RPE (p < 0.05). A greater CAT, GPX, and CuZnSOD enzymatic activity (p < 0.05) and increased nDNA protection (p < 0.05) were also observed. However, there was no adaptive benefit for mtDNA protection or repair in response to oxidative stress. This study confirms a role for the adaptive response as an important antioxidant defense for cells located in inherently oxidizing microenvironments. Furthermore, it identifies that the mitochondria are a weak link in otherwise efficient oxidative stress defenses and that this may contribute to aging and age-related disease.
authors.affiliation: Cell and Molecular Biology Unit, School of Optometry and Vision Sciences, Cardiff University, Cardiff CF10 3NB, UK.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Jarrett
authors.forename: Mike E
authors.initials: ME
authors.lastname: Boulton
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase