Increased "vigilance" of antioxidant mechanisms in neural stem cells potentiates their capability to resist oxidative stress

Lalitha Madhavan, Václav Ourednik, Jitka Ourednik

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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 post-mitotic 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.

Original languageEnglish (US)
Pages (from-to)2110-2119
Number of pages10
JournalStem Cells
Volume24
Issue number9
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Neural Stem Cells
Oxidative Stress
Antioxidants
Glutathione Peroxidase
Reactive Oxygen Species
Stem Cell Niche
Basal Metabolism
Central Nervous System Diseases
Prosencephalon
Oxidation-Reduction
Cell Survival
Up-Regulation
Central Nervous System
Cell Culture Techniques
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Increased "vigilance" of antioxidant mechanisms in neural stem cells potentiates their capability to resist oxidative stress. / Madhavan, Lalitha; Ourednik, Václav; Ourednik, Jitka.

In: Stem Cells, Vol. 24, No. 9, 2006, p. 2110-2119.

Research output: Contribution to journalArticle

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