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Background  Werner Syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS encodes a DNA helicase/exonuclease protein believed to affect different aspects of transcription, replication, and/or DNA repair. In addition to genomic instability, human WS cells exhibit oxidative stress. In this report, we have examined the impact of exogenous hydrogen peroxide on the expression profile of mouse embryonic fibroblasts lacking part of the helicase domain of the  WRN  homologue (here referred to as  Wrn  Δ hel /Δ hel  ).    Results   Wrn  Δ hel /Δ hel   mutant mouse embryonic fibroblasts exhibit increased oxidative stress. This was reflected by increased intracellular reactive oxygen species (ROS), increased oxidative damage in genomic DNA, changes in ATP/ADP ratios, and a disruption of the inner mitochondrial transmembrane potential when compared to wild type mouse embryonic fibroblasts. Expression profile analyses of hydrogen peroxide-treated wild type cells have indicated significant decreases in the expression of genes involved in mitosis, glycolysis, fatty acid metabolism, nucleic acid metabolism, and cell cycle control, as well as protein modification and stability. Such decreases in these biological processes were not observed in hydrogen peroxide-treated  Wrn  Δ hel /Δ hel   cells. Importantly, untreated  Wrn  Δ hel /Δ hel   cells already exhibited down regulation of several biological processes decreased in wild type cells that had been treated with hydrogen peroxide.    Conclusion  Expression profiling of  Wrn  Δ hel /Δ hel   mutant cells revealed a very different response to exogenous addition of hydrogen peroxide in culture compared to wild type cells. This is due in part to the fact that  Wrn  Δ hel /Δ hel   mutant cells already exhibited a modest chronic intracellular oxidative stress.

bmc genomics

Expression profiling of mouse embryonic fibroblasts with a deletion in the helicase domain of the Werner Syndrome gene homologue treated with hydrogen peroxide