Neurotoxicity Research

, Volume 13, Issue 3, pp 197–207

Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury

  • Simone Stark
  • Alexandra SchÜller
  • Marco Sifringer
  • Bettina Erstner
  • Felix Brehmer
  • Sven Weber
  • Rodica Altmann
  • Michael Obladen
  • Christoph BÜhrer
  • Ursula Felderhoff-Mueser
Article

DOI: 10.1007/BF03033503

Cite this article as:
Stark, S., SchÜller, A., Sifringer, M. et al. neurotox res (2008) 13: 197. doi:10.1007/BF03033503
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Abstract

Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in anin vitro model of hyperoxiainduced injury to immature oligodendrocytes.

Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 μM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed.

Suramin led to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling.

These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.

Keywords

HyperoxiaSuraminPeriventricular leukomalaciaWhite matter

Copyright information

© Springer 2008

Authors and Affiliations

  • Simone Stark
    • 1
    • 2
  • Alexandra SchÜller
    • 1
  • Marco Sifringer
    • 1
  • Bettina Erstner
    • 1
  • Felix Brehmer
    • 1
  • Sven Weber
    • 1
  • Rodica Altmann
    • 1
  • Michael Obladen
    • 1
  • Christoph BÜhrer
    • 3
  • Ursula Felderhoff-Mueser
    • 1
  1. 1.Department of Neonatology, Campus Virchow-Klinikum, CharitéUniversitätsmedizin BerlinBerlinGermany
  2. 2.Department of PediatricsCatholic Children’s Hospital WilhelmstiftHamburgGermany
  3. 3.Department of NeonatologyBasel University Children’s HospitalBaselSwitzerland