The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells
Open accessAbstract
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.
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Cited by
Cellular mechanisms and physiological consequences of redox-dependent signalling
Holmström, K. M., & Finkel, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3801 · Cited by 2,093
Metabolic Regulation of Hematopoietic Stem Cells in the Hypoxic Niche
Suda, T., Takubo, K., & Semenza, G. L. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.09.010 · Cited by 844
Braganza, J. M., Lee, S. H., McCloy, R. F., & McMahon, M. J. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61852-1 · Cited by 469
Kell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361
Keeley, T. P., & Mann, G. E. (2019) · Physiological Reviews · doi:10.1152/physrev.00041.2017 · Cited by 329
Metadata
- Authors
- Li, T.-S., & Marbán, E.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-04
- Volume
- 28
- Issue
- 7
- Pages
- 1178-1185
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2084690414
- Cited by
- 171
- References
- 6
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Funders
- NIH (R01HL083109)
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