Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells
Open Access
- 4 May 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 28 (7), 1178-1185
- https://doi.org/10.1002/stem.438
Abstract
Stem cell cytogenetic abnormalities constitute a roadblock to regenerative therapies. We investigated the possibility that reactive oxygen species (ROSs) influence genomic stability in cardiac and embryonic stem cells. Karyotypic abnormalities in primary human cardiac stem cells were suppressed by culture in physiological (5%) oxygen, but addition of antioxidants to the medium unexpectedly increased aneuploidy. Intracellular ROS levels were moderately decreased in physiological oxygen, but dramatically decreased by the addition of high-dose antioxidants. Quantification of DNA damage in cardiac stem cells and in human embryonic stem cells revealed a biphasic dose-dependence: antioxidants suppressed DNA damage at low concentrations, but potentiated such damage at higher concentrations. High-dose antioxidants decreased cellular levels of ATM (ataxia-telangiectasia mutated) and other DNA repair enzymes, providing a potential mechanistic basis for the observed effects. These results indicate that physiological levels of intracellular ROS are required to activate the DNA repair pathway for maintaining genomic stability in stem cells. The concept of an “oxidative optimum” for genomic stability has broad implications for stem cell biology and carcinogenesis. STEM CELLS 2010;28:1178–1185Keywords
Funding Information
- NIH (R01HL083109)
This publication has 33 references indexed in Scilit:
- Chromosome 7 and 19 Trisomy in Cultured Human Neural Progenitor CellsPLOS ONE, 2009
- Validation of the Cardiosphere Method to Culture Cardiac Progenitor Cells from Myocardial TissuePLOS ONE, 2009
- A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafishNature, 2009
- Reduced tumorigenesis in p53 knockout mice exposed in utero to low‐dose vitamin ECancer, 2009
- ATM-mediated Transcriptional Elevation of Prion in Response to Copper-induced Oxidative StressOnline Journal of Public Health Informatics, 2009
- Vitamins E and C in the Prevention of Cardiovascular Disease in MenJama-Journal Of The American Medical Association, 2008
- Human αB-Crystallin Mutation Causes Oxido-Reductive Stress and Protein Aggregation Cardiomyopathy in MiceCell, 2007
- High-Dose α-Tocopherol Therapy Does Not Affect HDL Subfractions in Patients with Coronary Artery Disease on Statin TherapyClinical Chemistry, 2007
- Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary PreventionJama-Journal Of The American Medical Association, 2007
- Reactive oxygen species produced by NADPH oxidase regulate plant cell growthNature, 2003