Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics

You have full text access to this OnlineOpen article

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

  1. Tao-Sheng Li¶,*,
  2. Eduardo Marbán*

Article first published online: 4 MAY 2010

DOI: 10.1002/stem.438

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 7, pages 1178–1185, July 2010

Additional Information

How to Cite

Li, T.-S. and Marbán, E. (2010), Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells. STEM CELLS, 28: 1178–1185. doi: 10.1002/stem.438

Author Information

  1. The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

  1. Telephone: +44(0)20 79052121; Fax: +44(0)20 78314366

*The Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, California 90048, USA

  1. †

    Author contributions: T.-S.L.: conception and design, manuscript writing, collection and/or assembly of data, data analysis and interpretation; E.M.: conception and design, manuscript writing, financial support, final approval of manuscript.

  2. ‡

    First published online in STEM CELLSEXPRESS May 4, 2010.

  3. §

    Disclosure of potential conflicts of interest is found at the end of this article.

Publication History

  1. Issue published online: 20 JUL 2010
  2. Article first published online: 4 MAY 2010
  3. Manuscript Accepted: 21 APR 2010
  4. Manuscript Received: 22 FEB 2010

Funded by

  • NIH. Grant Number: R01HL083109

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (1621K)

Keywords:

  • Reactive oxygen species;
  • Genomic stability;
  • DNA repair;
  • Stem cells

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;28:1178–1185

View Full Article with Supporting Information (HTML) Get PDF (1621K)