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

BMC Genomics

Research Article

Chantal Garand¹  Adam Labbé¹  Michel Lebel¹  Ramachander VN Turaga¹  Éric R Paquet¹ 

[1] Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, Québec, Canada;

关键词: Wild Type Cell;    Mouse Embryonic Fibroblast;    Intracellular Reactive Oxygen Species Level;    Mitochondrial Transmembrane Potential;    Werner Syndrome;   

DOI  :  10.1186/1471-2164-11-127

 received in 2009-11-17, accepted in 2010-02-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundWerner 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 WrnΔhel/Δhel).ResultsWrnΔhel/Δhelmutant 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 WrnΔhel/Δhelcells. Importantly, untreated WrnΔhel/Δhelcells already exhibited down regulation of several biological processes decreased in wild type cells that had been treated with hydrogen peroxide.ConclusionExpression profiling of WrnΔhel/Δhelmutant 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 WrnΔhel/Δhelmutant cells already exhibited a modest chronic intracellular oxidative stress.

【 授权许可】

Unknown   
© Labbé et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.