HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0018v1 24/9/2110    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Madhavan, L. Articles by Ourednik, J. Search for Related Content PubMed PubMed Citation Articles by Madhavan, L. Articles by Ourednik, J.

TISSUE-SPECIFIC STEM CELLS

Increased "Vigilance" of Antioxidant Mechanisms in Neural Stem Cells Potentiates Their Capability to Resist Oxidative Stress

Department of Biomedical Sciences, Iowa State University, Ames, Iowa, USA

Key Words. Antioxidants • Central nervous system • 3-Nitropropionic acid • Mitochondrial activity • Reactive oxygen species • Redox • Neuroprotection • Neural stem cells • Cell interaction • In vitro • In vivo • Superoxide dismutase 2Uncoupling protein 2 • Glutathione peroxidase • Catalase

Correspondence: Jitka Ourednik, Ph.D., Department of Biomedical Sciences, College of Veterinary Medicine 2052, Ames, Iowa 50011, USA. Telephone: 515-294-6449; Fax: 515-294-6449; e-mail: joured{at}iastate.edu

Received January 9, 2006; accepted for publication May 16, 2006.
First published online in STEM CELLS EXPRESS   May 25, 2006.



Although the potential value of transplanted and endogenous neural stem cells (NSCs) for the treatment of the impaired central nervous system (CNS) has widely been accepted, almost nothing is known about their sensitivity to the hostile microenvironment in comparison to surrounding, more mature cell populations. Since many neuropathological insults are accompanied by oxidative stress, this report compared the alertness of antioxidant defense mechanisms and cell survival in NSCs and postmitotic neural cells (PNCs). Both primary and immortalized cells were analyzed. At steady state, NSCs distinguished themselves in their basal mitochondrial metabolism from PNCs by their lower reactive oxygen species (ROS) levels and higher expression of the key antioxidant enzymes uncoupling protein 2 (UCP2) and glutathione peroxidase (GPx). Following exposure to the mitochondrial toxin 3-nitropropionic acid, PNC cultures were marked by rapidly decreasing mitochondrial activity and increasing ROS content, both entailing complete cell loss. NSCs, in contrast, reacted by fast upregulation of UCP2, GPx, and superoxide dismutase 2 and successfully recovered from an initial deterioration. This recovery could be abolished by specific antioxidant inhibition. Similar differences between NSCs and PNCs regarding redox control efficiency were detected in both primary and immortalized cells. Our first in vivo data from the subventricular stem cell niche of the adult mouse forebrain corroborated the above observations and revealed strong baseline expression of UCP2 and GPx in the resident, proliferating NSCs. Thus, an increased "vigilance" of antioxidant mechanisms might represent an innate characteristic of NSCs, which not only defines their cell fate, but also helps them to encounter oxidative stress in diseased CNS.

This article has been cited by other articles:

				L. Madhavan, V. Ourednik, and J. Ourednik Neural Stem/Progenitor Cells Initiate the Formation of Cellular Networks That Provide Neuroprotection by Growth Factor-Modulated Antioxidant Expression Stem Cells, January 1, 2008; 26(1): 254 - 265. [Abstract] [Full Text] [PDF]

				H.-L. Chen, F. Pistollato, D. J. Hoeppner, H.-T. Ni, R. D.G. McKay, and D. M. Panchision Oxygen Tension Regulates Survival and Fate of Mouse Central Nervous System Precursors at Multiple Levels Stem Cells, September 1, 2007; 25(9): 2291 - 2301. [Abstract] [Full Text] [PDF]