Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells

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 c...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2010-07, Vol.28 (7), p.1178-1185
Main Authors: Li, Tao‐Sheng, Marbán, Eduardo
Format: Article
Language:English
Subjects:
Antioxidants - pharmacology
Cells, Cultured
DNA Damage
DNA repair
Genomic Instability
Genomic stability
Humans
Intracellular Space - metabolism
Oxygen - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
Stem cells
Stem Cells - drug effects
Stem Cells - metabolism
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Summary: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;28:1178–1185
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.438